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Gene Information

Gene symbol: IV

Gene name: inversus situs, viscerum

HGNC ID: 6185

Related Genes

# Gene Symbol Number of hits
1 AD5 1 hits
2 ADRM1 1 hits
3 AGTR2 1 hits
4 CAT 1 hits
5 CCL22 1 hits
6 CCL3 1 hits
7 CCL4 1 hits
8 CCL5 1 hits
9 CCR5 1 hits
10 CCR7 1 hits
11 CD28 1 hits
12 CD4 1 hits
13 CD40 1 hits
14 CD40LG 1 hits
15 CD46 1 hits
16 CD55 1 hits
17 CD59 1 hits
18 CD69 1 hits
19 CD79A 1 hits
20 CD8A 1 hits
21 CELIAC3 1 hits
22 CSF1 1 hits
23 CSF2 1 hits
24 CTLA4 1 hits
25 CXCR4 1 hits
26 CXCR6 1 hits
27 DDX58 1 hits
28 E11S 1 hits
29 ENG 1 hits
30 ENPEP 1 hits
31 ERG 1 hits
32 ERVWE1 1 hits
33 FAS 1 hits
34 GSTA1 1 hits
35 GZMB 1 hits
36 HAVCR2 1 hits
37 HLA-A 1 hits
38 HSP90B1 1 hits
39 HSPA1A 1 hits
40 IFNA1 1 hits
41 IFNG 1 hits
42 IL12A 1 hits
43 IL15 1 hits
44 IL2 1 hits
45 IL3 1 hits
46 IL4 1 hits
47 IL6ST 1 hits
48 IL7 1 hits
49 JAG1 1 hits
50 KIR3DL1 1 hits
51 LAMP1 1 hits
52 MICB 1 hits
53 MRPL28 1 hits
54 NFKB1 1 hits
55 NRSN1 1 hits
56 PCSK7 1 hits
57 PDCD1 1 hits
58 POLE3 1 hits
59 PSMD9 1 hits
60 PTPN11 1 hits
61 S100B 1 hits
62 SP1 1 hits
63 TH1L 1 hits
64 TNF 1 hits
65 TNPO1 1 hits
66 TRPV6 1 hits
67 VAULTRC1 1 hits
68 VHLL 1 hits

Related Sentences

# PMID Sentence
1 1372038 Mice were immunized with SMAA complexes containing recombinant p27-TAG and MAbs have been isolated that recognized native SIV p27.
2 1708168 Recombinant virus vaccine-induced SIV-specific CD8+ cytotoxic T lymphocytes.
3 1719081 We have examined the induction and epitope specificity of T cells for the simian immunodeficiency virus (SIV) gag p27 protein in macaques immunized with either a recombinant SIV gag protein or an inactivated SIV vaccine.
4 1719081 CD4+ MHC class II-restricted T cell lines and clones derived from five immunized macaques recognized a total of seven peptides in three immunodominant regions of p27.
5 1719081 Although this epitope is in a conserved region of the gag protein of SIV, its recognition by a CD4+ T cell clone was abrogated by sequence variation in the equivalent HIV protein.
6 1719081 We have examined the induction and epitope specificity of T cells for the simian immunodeficiency virus (SIV) gag p27 protein in macaques immunized with either a recombinant SIV gag protein or an inactivated SIV vaccine.
7 1719081 CD4+ MHC class II-restricted T cell lines and clones derived from five immunized macaques recognized a total of seven peptides in three immunodominant regions of p27.
8 1719081 Although this epitope is in a conserved region of the gag protein of SIV, its recognition by a CD4+ T cell clone was abrogated by sequence variation in the equivalent HIV protein.
9 2498082 With the use of a sensitive sequence comparison algorithm, a homology has been suggested between the primary structures of simian immunodeficiency virus (SIV) p24 core protein and foot-and-mouth disease virus (FMD) VP2 coat protein.
10 7502858 Macaques were immunized with a recombinant, particulate SIV antigen (SIV gag P27), covalently linked to the mucosal adjuvant cholera toxin B subunit (CTB).
11 7502858 The results show that both vaginal followed by oral immunization or the reverse sequence induces specific p27 IgA and IgG antibodies in the vaginal fluid and serum.
12 7502859 T cell responses in macaques after vaginal immunization with particulate SIV p27 antigen.
13 7526538 Complement control proteins, CD46, CD55, and CD59, as common surface constituents of human and simian immunodeficiency viruses and possible targets for vaccine protection.
14 7526538 Three complement control proteins, CD46 (membrane cofactor protein), CD55 (decay accelerating protein), and CD59 (HRF20), were found by flow cytometry to be expressed on the surface of CD4+ cell lines commonly used for HIV-1 and SIV synthesis.
15 7526538 Monoclonal antibodies to each of these proteins precipitated HIV-1 IIIB and SIV delta/B670 synthesized in CEM x 174 cells and two primary HIV-1 isolates synthesized in peripheral blood mononuclear cells, indicating that CD46, CD55, and CD59 are physically associated with the virus membrane after the virus has been released from the surface of infected cells.
16 7526538 Evidence that CD46 and CD59 are immunogenic in macaques was found when anti-cell antibodies in plasmas from macaques immunized with human cell-grown SIV blocked anti-CD46 and anti-CD59 from binding to the surface of CEM x 174 cells.
17 7526538 These results demonstrate that CD46, CD55, and CD59 are common surface constituents of HIV-1 and SIV.
18 7571408 In contrast to monkeys infected with pathogenic SIV, pC8-infected macaques developed a virus-specific T-cell proliferation.
19 7584989 Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated macaques.
20 7848685 Fine analysis of humoral antibody response to envelope glycoprotein of SIV in infected and vaccinated macaques.
21 7848685 To characterize the serological response to SIV envelope, induced by vaccination with different envelope immunogens or by SIV infection, plasma samples from 11 cynomolgus macaques infected with simian immunodeficiency virus (SIV) and from 16 macaques vaccinated with three different recombinant envelope proteins were analyzed by (1) ELISA, using a variety of antigens including overlapping peptides encompassing the entire sequence of the envelope protein of SIV, and (2) competition assays, using neutralizing monoclonal antibodies to SIV gp120.
22 7848685 Fine analysis of humoral antibody response to envelope glycoprotein of SIV in infected and vaccinated macaques.
23 7848685 To characterize the serological response to SIV envelope, induced by vaccination with different envelope immunogens or by SIV infection, plasma samples from 11 cynomolgus macaques infected with simian immunodeficiency virus (SIV) and from 16 macaques vaccinated with three different recombinant envelope proteins were analyzed by (1) ELISA, using a variety of antigens including overlapping peptides encompassing the entire sequence of the envelope protein of SIV, and (2) competition assays, using neutralizing monoclonal antibodies to SIV gp120.
24 7865316 Challenge of the SIV gp130-immunized monkeys with the spleen-derived virus led to infection of three animals; remarkably, one of these was only PCR positive.
25 7865316 However, neutralizing antibodies may have been important in the SIV gp130-immunized animals at first challenge.
26 7865316 Challenge of the SIV gp130-immunized monkeys with the spleen-derived virus led to infection of three animals; remarkably, one of these was only PCR positive.
27 7865316 However, neutralizing antibodies may have been important in the SIV gp130-immunized animals at first challenge.
28 8074930 Proteins expressed from pGEXcPk and pQ9cPk had a short oligopeptide tag termed Pk at their carboxy termini and either glutathione S-transferase (GST) or a small histidine (His) tag, respectively, at their N termini.
29 8074930 The genes for nef, endonuclease, p15, p17, p27, protease, Rev, reverse transcriptase (rt), tat, vif, vpr, and vpx of simian immunodeficiency virus (SIV mac 251) were cloned and expressed as both GST-SIV-Pk and His-SIV-Pk proteins.
30 8074930 Antibodies to endonuclease, p15, p17, p27, rt, and vif were readily detected, antibodies against protease and vpx were present at much lower levels, but no antibodies were detected to nef, rev, tat, or vpr.
31 8133061 Seven lipopeptides were synthesized, derived from known immunogenic regions of the simian immunodeficiency virus (SIV) NEF and GAG proteins.
32 8178558 In this way, immune complexes containing the p17, p27, vpr and vpx proteins of simian immunodeficiency virus (SIV) have been purified.
33 8574147 The majority of the clones expressed SIV p27 antigen and low levels of virus reverse transcriptase activity.
34 8574147 Western blot analysis, performed with either monoclonal or polyclonal sera, showed that a chronically infected clone (B7) produced particles which contained envelope (gp135 and gp43), gag precursors and gag proteins (p27, p16 and p8).
35 8578803 Immunization studies in rats showed that this protein was also less efficient in inducing antibodies against this antigenic site, and that it induced significantly lower levels of virus neutralizing antibodies than the other SIV-envelope glycoprotein.
36 8578803 The immunogenicity of the SIV-envelope glycoprotein incorporated into immune stimulating complexes (iscoms) was compared to that of the same protein presented with Quil A or MDP-tsl.
37 8578803 Immunization studies in rats showed that this protein was also less efficient in inducing antibodies against this antigenic site, and that it induced significantly lower levels of virus neutralizing antibodies than the other SIV-envelope glycoprotein.
38 8578803 The immunogenicity of the SIV-envelope glycoprotein incorporated into immune stimulating complexes (iscoms) was compared to that of the same protein presented with Quil A or MDP-tsl.
39 8642649 Expression of IFN-gamma by SIV(HyIFN) reached levels as high as 10(6) U/ml after 11 days in culture.
40 8763998 Detection of simian immunodeficiency virus (SIV)-specific CD8+ T cells in macaques protected from SIV challenge by prior SIV subunit vaccination.
41 8763998 Peripheral blood mononuclear cells were obtained from the protected macaques and analyzed for CD8+ cytotoxic T-lymphocyte (CTL) responses to SIV proteins.
42 8763998 These CTL, as reflected by studies of cytolytic lines and derived T-cell clones, were CD8+, did not recognize allogeneic targets, and recognized the SIV proteins in the context of class I major histocompatibility complex molecules.
43 8763998 The frequency of precursor CD8+ CTL reactive to SIV proteins was determined by limiting-dilution analysis and demonstrated that the responses elicited following challenge of protected animals to SIV proteins not present in the vaccine were quantitatively similar to those of animals persistently infected with SIV.
44 8763998 The presence of these CD8+ CTL responses to SIV proteins present only in the challenge virus suggests that infection of some host cells occurred postchallenge.
45 8763998 Detection of simian immunodeficiency virus (SIV)-specific CD8+ T cells in macaques protected from SIV challenge by prior SIV subunit vaccination.
46 8763998 Peripheral blood mononuclear cells were obtained from the protected macaques and analyzed for CD8+ cytotoxic T-lymphocyte (CTL) responses to SIV proteins.
47 8763998 These CTL, as reflected by studies of cytolytic lines and derived T-cell clones, were CD8+, did not recognize allogeneic targets, and recognized the SIV proteins in the context of class I major histocompatibility complex molecules.
48 8763998 The frequency of precursor CD8+ CTL reactive to SIV proteins was determined by limiting-dilution analysis and demonstrated that the responses elicited following challenge of protected animals to SIV proteins not present in the vaccine were quantitatively similar to those of animals persistently infected with SIV.
49 8763998 The presence of these CD8+ CTL responses to SIV proteins present only in the challenge virus suggests that infection of some host cells occurred postchallenge.
50 8763998 Detection of simian immunodeficiency virus (SIV)-specific CD8+ T cells in macaques protected from SIV challenge by prior SIV subunit vaccination.
51 8763998 Peripheral blood mononuclear cells were obtained from the protected macaques and analyzed for CD8+ cytotoxic T-lymphocyte (CTL) responses to SIV proteins.
52 8763998 These CTL, as reflected by studies of cytolytic lines and derived T-cell clones, were CD8+, did not recognize allogeneic targets, and recognized the SIV proteins in the context of class I major histocompatibility complex molecules.
53 8763998 The frequency of precursor CD8+ CTL reactive to SIV proteins was determined by limiting-dilution analysis and demonstrated that the responses elicited following challenge of protected animals to SIV proteins not present in the vaccine were quantitatively similar to those of animals persistently infected with SIV.
54 8763998 The presence of these CD8+ CTL responses to SIV proteins present only in the challenge virus suggests that infection of some host cells occurred postchallenge.
55 8763998 Detection of simian immunodeficiency virus (SIV)-specific CD8+ T cells in macaques protected from SIV challenge by prior SIV subunit vaccination.
56 8763998 Peripheral blood mononuclear cells were obtained from the protected macaques and analyzed for CD8+ cytotoxic T-lymphocyte (CTL) responses to SIV proteins.
57 8763998 These CTL, as reflected by studies of cytolytic lines and derived T-cell clones, were CD8+, did not recognize allogeneic targets, and recognized the SIV proteins in the context of class I major histocompatibility complex molecules.
58 8763998 The frequency of precursor CD8+ CTL reactive to SIV proteins was determined by limiting-dilution analysis and demonstrated that the responses elicited following challenge of protected animals to SIV proteins not present in the vaccine were quantitatively similar to those of animals persistently infected with SIV.
59 8763998 The presence of these CD8+ CTL responses to SIV proteins present only in the challenge virus suggests that infection of some host cells occurred postchallenge.
60 8763998 Detection of simian immunodeficiency virus (SIV)-specific CD8+ T cells in macaques protected from SIV challenge by prior SIV subunit vaccination.
61 8763998 Peripheral blood mononuclear cells were obtained from the protected macaques and analyzed for CD8+ cytotoxic T-lymphocyte (CTL) responses to SIV proteins.
62 8763998 These CTL, as reflected by studies of cytolytic lines and derived T-cell clones, were CD8+, did not recognize allogeneic targets, and recognized the SIV proteins in the context of class I major histocompatibility complex molecules.
63 8763998 The frequency of precursor CD8+ CTL reactive to SIV proteins was determined by limiting-dilution analysis and demonstrated that the responses elicited following challenge of protected animals to SIV proteins not present in the vaccine were quantitatively similar to those of animals persistently infected with SIV.
64 8763998 The presence of these CD8+ CTL responses to SIV proteins present only in the challenge virus suggests that infection of some host cells occurred postchallenge.
65 8827215 Cytotoxic T lymphocytes to SIV Nef and RT were demonstrable in one of four SHIV-infected monkeys before SIVsm challenge, but this monkey was not protected against SIV infection.
66 9032366 Specific SIV Nef peptide proliferative responses and cytokine production were observed.
67 9135877 The IL-2-expressing SIV had been previously constructed to enhance the immunogenicity of live attenuated SIV vaccines.
68 9164952 Rhesus macaques were orally immunized with a mucosal vaccine consisting of two different concentrations (1 mg vs 250 microg) of recombinant SIV p55gag (p55) with or without cholera toxin (CT, 50 microg) as a mucosal adjuvant.
69 9164952 When culture supernatants from these p55-stimulated PBMCs were examined for Th1 (IFN-gamma) and Th2 (IL-4 and IL-10) cytokines, both IFN-gamma and IL-10 were present, but IL-4 was absent.
70 9164952 CD4+ T cells isolated from these p55-stimulated PBMCs contained IFN-gamma spot-forming cells (SFCs) but not IL-4 SFCs.
71 9164952 These results were further confirmed by cytokine-specific reverse transcriptase PCR analysis, where p55-specific CD4+ T cells expressed mRNA for IFN-gamma, IL-6, and IL-10, but not IL-4.
72 9164952 These findings suggest that oral immunization of nonhuman primates induced both IFN-gamma-secreting Th1 and select Th2 cytokine (e.g., IL-6 and IL-10)-producing CD4+ Th cells, which accounted for the generation of p55-specific systemic and mucosal Ab responses.
73 9268165 Like the SIV(mac)LG1-inoculated macaques, these animals also resisted SHIV(KU-1) challenge as judged by the inability to recover infectious virus, normal CD4+ T cell counts, and the absence of SHIV(KU-1) signature sequences in the lymph node tissue.
74 9286055 Selective activation of CD8+ and MHC-restricted SIV Gag-specific CTL was induced by stimulation with autologous para-formaldehyde-fixed B-lymphoblastoid cell lines infected with a recombinant vaccinia virus expressing SIV Gag.
75 9419166 Induction of Th2 cytokine expression for p27-specific IgA B cell responses after targeted lymph node immunization with simian immunodeficiency virus antigens in rhesus macaques.
76 9419166 In addition, a peak of SIV-specific IgA B cell responses was noted following the third immunization.
77 9430249 Because a broad immune response directed to multiple HIV/SIV antigens is highly desirable in order to develop effective vaccines, we have also investigated the immune response induced by an rBCG strain expressing a large N-terminal portion of the SIVmac251 Env gp110-encoding gene.
78 9445041 In two macaques immunized with a mixture of lipopeptides derived from simian immunodeficiency virus (SIV) Nef and Gag proteins, CTL responses were directed against the same, single epitope of the Nef protein (amino acids 128 to 137) presenting an alanine at position 136 (Nef 128-137/136A).
79 9445041 Dose analysis of peptides used to sensitize target cells as well as a major histocompatibility complex (MHC)-peptide stability assay suggested that the selected peptide Nef 128-137/136T has an altered capacity to bind to the MHC.
80 9554279 Protection was associated with significant increase in the iliac lymph nodes IgA antibody secreting cells to p27 (p < 0.02), CD8-suppressor factor inhibiting replication of SIV in CD4+ T cells (p < 0.01) and the chemokines RANTES and MIP-1 beta (p < 0.01).
81 9658070 CD8(+) T lymphocytes from immunized animals were able to potently suppress SIV replication in autologous SIV-infected CD4(+) T cells.
82 9658070 Suppression of SIV replication by unstimulated CD8(+) T cells required direct contact and was major histocompatibility complex (MHC) restricted.
83 9658070 However, CD3-stimulated CD8(+) T cells produced soluble factors that inhibited SIV replication in an MHC-unrestricted fashion as much as 30-fold.
84 9658070 Supernatants from stimulated CD8(+) T cells were also able to inhibit replication of both CCR5- and CXCR4-dependent human immunodeficiency virus type 1 (HIV-1) strains.
85 9658070 Production of RANTES, macrophage inhibitory protein 1alpha (MIP-1alpha), or MIP-1beta from stimulated CD8(+) T cells of vaccinated animals was almost 10-fold higher than that from stimulated CD8(+) T cells of control animals.
86 9658070 Our results indicate that inhibition of SIV replication by CD8(+) T cells from animals immunized with live attenuated SIV strains involves both MHC-restricted and -unrestricted mechanisms and that MHC-unrestricted inhibition of SIV replication is due principally to soluble factors other than RANTES, MIP-1alpha, and MIP-1beta.
87 9658070 CD8(+) T lymphocytes from immunized animals were able to potently suppress SIV replication in autologous SIV-infected CD4(+) T cells.
88 9658070 Suppression of SIV replication by unstimulated CD8(+) T cells required direct contact and was major histocompatibility complex (MHC) restricted.
89 9658070 However, CD3-stimulated CD8(+) T cells produced soluble factors that inhibited SIV replication in an MHC-unrestricted fashion as much as 30-fold.
90 9658070 Supernatants from stimulated CD8(+) T cells were also able to inhibit replication of both CCR5- and CXCR4-dependent human immunodeficiency virus type 1 (HIV-1) strains.
91 9658070 Production of RANTES, macrophage inhibitory protein 1alpha (MIP-1alpha), or MIP-1beta from stimulated CD8(+) T cells of vaccinated animals was almost 10-fold higher than that from stimulated CD8(+) T cells of control animals.
92 9658070 Our results indicate that inhibition of SIV replication by CD8(+) T cells from animals immunized with live attenuated SIV strains involves both MHC-restricted and -unrestricted mechanisms and that MHC-unrestricted inhibition of SIV replication is due principally to soluble factors other than RANTES, MIP-1alpha, and MIP-1beta.
93 9733821 To modulate the antiviral immune response induced by live attenuated SIV vaccines, we had previously infected rhesus monkeys with a nef deletion mutant of SIV expressing interleukin 2 (SIV-IL2) (B.
94 9733821 Since the SIV-MLV hybrid uses the MLV Env receptor Pit2 and not CD4 and a coreceptor for virus entry, chemokine inhibition and receptor interference phenomena were not involved in protection.
95 9788676 Five male-female pairs of macaques were inoculated intrarectally with SIV(Mne) E11S, a biological clone, and serially euthanized at 1, 2, 4, 8, and 12 weeks postinoculation.
96 9788676 The most dramatic increases in both total and SIV-specific IgA levels were detected in rectal secretion samples.
97 9788676 Five male-female pairs of macaques were inoculated intrarectally with SIV(Mne) E11S, a biological clone, and serially euthanized at 1, 2, 4, 8, and 12 weeks postinoculation.
98 9788676 The most dramatic increases in both total and SIV-specific IgA levels were detected in rectal secretion samples.
99 9834076 Female rhesus macaques were nasally immunized with p55gag (p55) of SIV and cholera toxin as a mucosal adjuvant.
100 9834076 Furthermore, high numbers of p55-specific IgA and IgG Ab-forming cells were induced in mucosal effector sites, i.e., uterine cervix, intestinal lamina propria, and nasal passage. p55-specific CD4+ T cells in both systemic and mucosal compartments expressed IFN-gamma and IL-2 (Th1-type)- as well as IL-5, IL-6, and IL-10 (Th2-type)-specific mRNA.
101 9834076 These results show that nasal immunization with SIV p55 with cholera toxin elicits both Th1- and selective Th2-type cytokine responses associated with the induction of SIV-specific mucosal and serum Abs, and CTL activity.
102 9834076 Female rhesus macaques were nasally immunized with p55gag (p55) of SIV and cholera toxin as a mucosal adjuvant.
103 9834076 Furthermore, high numbers of p55-specific IgA and IgG Ab-forming cells were induced in mucosal effector sites, i.e., uterine cervix, intestinal lamina propria, and nasal passage. p55-specific CD4+ T cells in both systemic and mucosal compartments expressed IFN-gamma and IL-2 (Th1-type)- as well as IL-5, IL-6, and IL-10 (Th2-type)-specific mRNA.
104 9834076 These results show that nasal immunization with SIV p55 with cholera toxin elicits both Th1- and selective Th2-type cytokine responses associated with the induction of SIV-specific mucosal and serum Abs, and CTL activity.
105 9870315 A cocktail of Mycobacterium bovis BCG recombinants expressing the SIV Nef, Env, and Gag antigens induces antibody and cytotoxic responses in mice vaccinated by different mucosal routes.
106 9886431 Another transiently infected monkey had SIV-specific IgA secreting B cells in the LP.
107 10196344 We have optimized the induction of antiviral cytotoxic T lymphocytes (CTL) in rhesus macaques by a lipopeptide vaccine containing seven peptides from simian immunodeficiency virus (SIV) Nef and Gag proteins and a strong T-helper peptide from tetanus toxoid (TT) that is promiscuous in humans (peptide TT 830-846).
108 10386338 Additionally, a Nef-deleted SIV virus has low titres in rhesus monkeys and the animals develop AIDS at a much slower rate.
109 10386338 In vitro, Nef can exert at least three kinds of effects: it downregulates CD4 and MHC class I, it stimulates virion infectivity and it alters signal transduction pathways.
110 10386338 To accomplish this, Nef interacts with a series of cellular partners including CD4, components of the adaptor complexes AP-1 and AP-2, and several protein kinases, Nef often functioning as a connector between targets and effectors.
111 10501490 A second group were primed twice with recombinant vaccinia virus expressing SIV gp160 and then boosted twice with recombinant SIV gp120.
112 10516057 We report the construction of recombinant vectors of two different serotypes of poliovirus-expressing simian immunodeficiency virus (SIV) antigens and the intranasal and intravenous inoculations of four adult cynomolgus macaques with these poliovirus vectors expressing the SIV proteins p17(gag) and gp41(env).
113 10570193 To better understand the role that CD4(+) T helper responses may play in mediating protection in this model, we characterized SIV-specific proliferative and cytokine responses in macaques immunized with live attenuated SIV strains.
114 10570193 SIV-specific stimulation of lymphocytes from vaccinated macaques resulted in secretion of interferon-gamma, IL-2, regulated-upon-activation, normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta but not IL-4 or IL-10.
115 10570193 Intracellular flow cytometric analysis documented that, in macaques vaccinated with SIVmac239Deltanef, up to 2% of all CD4(+)T cells were specific for SIV p55.
116 10570193 To better understand the role that CD4(+) T helper responses may play in mediating protection in this model, we characterized SIV-specific proliferative and cytokine responses in macaques immunized with live attenuated SIV strains.
117 10570193 SIV-specific stimulation of lymphocytes from vaccinated macaques resulted in secretion of interferon-gamma, IL-2, regulated-upon-activation, normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta but not IL-4 or IL-10.
118 10570193 Intracellular flow cytometric analysis documented that, in macaques vaccinated with SIVmac239Deltanef, up to 2% of all CD4(+)T cells were specific for SIV p55.
119 10593490 Characterization of SIV-specific CD4+ T-helper proliferative responses in macaques immunized with live-attenuated SIV.
120 10593490 SIV-specific proliferative responses were mediated by CD4+ T cells and were major histocompatibility (MHC) class II restricted.
121 10593490 Intracellular flow-cytometric analysis demonstrated the production of interleukin (IL)-2, interferon (IFN)-gamma, RANTES and macrophage inhibitory protein-1alpha (MIP-1alpha) by T lymphocytes from SIVmac239deltanef-vaccinated animals following SIV p55 stimulation.
122 10593490 Characterization of SIV-specific CD4+ T-helper proliferative responses in macaques immunized with live-attenuated SIV.
123 10593490 SIV-specific proliferative responses were mediated by CD4+ T cells and were major histocompatibility (MHC) class II restricted.
124 10593490 Intracellular flow-cytometric analysis demonstrated the production of interleukin (IL)-2, interferon (IFN)-gamma, RANTES and macrophage inhibitory protein-1alpha (MIP-1alpha) by T lymphocytes from SIVmac239deltanef-vaccinated animals following SIV p55 stimulation.
125 10683331 The kinetics of specific immune responses in rhesus monkeys inoculated with live recombinant BCG expressing SIV Gag, Pol, Env, and Nef proteins.
126 10683331 The immunogenicity of four recombinant BCG constructs expressing simian immunodeficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques.
127 10683331 A single simultaneous inoculation of all four recombinants elicited SIV-specific IgA and IgG antibody, and cellular immune responses, including CTL and helper T cell proliferation.
128 10683331 The kinetics of specific immune responses in rhesus monkeys inoculated with live recombinant BCG expressing SIV Gag, Pol, Env, and Nef proteins.
129 10683331 The immunogenicity of four recombinant BCG constructs expressing simian immunodeficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques.
130 10683331 A single simultaneous inoculation of all four recombinants elicited SIV-specific IgA and IgG antibody, and cellular immune responses, including CTL and helper T cell proliferation.
131 10683331 The kinetics of specific immune responses in rhesus monkeys inoculated with live recombinant BCG expressing SIV Gag, Pol, Env, and Nef proteins.
132 10683331 The immunogenicity of four recombinant BCG constructs expressing simian immunodeficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques.
133 10683331 A single simultaneous inoculation of all four recombinants elicited SIV-specific IgA and IgG antibody, and cellular immune responses, including CTL and helper T cell proliferation.
134 10710211 We have produced and characterized, in a baculovirus expression system, simian-human immunodeficiency virus-like particles (SHIV VLPs) containing SIV Gag and HIV envelope (Env) proteins.
135 10869776 We generated a chimeric SIV, FMSIV, by replacing SIV env with ecotropic Friend murine leukemia virus (FMLV) env to confine its replication to FMLV receptor (mCAT1)-expressing cells.
136 10888354 The inhibition of CD4+ cell depletion was associated with maintaining the proliferative response of helper T-cells against SIV p27 in the previously nonpathogenic virus-inoculated animals following the pathogenic virus challenge.
137 10888354 Furthermore, the decline of CD28+ cells, the increase in CD95+ cells, and the enhancement of in vitro apoptosis in PBMC were inhibited in the non-pathogenic virus-inoculated animals.
138 11044096 Upon rectal challenge with cloned SIVmac239, resistance to infection was observed, but some animals with high SIV-specific IgA levels in rectal secretions became infected.
139 11090194 In the long-term study, most of the immunized animals had low or undetectable postacute levels of plasma SIV RNA, and no CD4(+) T-cell depletion or clinical evidence of progressive disease, over more than 2 years of observation.
140 11134287 To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8(+) epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule.
141 11134287 We had previously identified the peptide binding motif of Mamu-A*01(2), a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM).
142 11134287 To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8(+) epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule.
143 11134287 We had previously identified the peptide binding motif of Mamu-A*01(2), a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM).
144 11289799 First, HIV and SIV infect CD4(+)targets such as helper T lymphocytes and macrophages, that is, cells that normally play an essential role in the emergence and maintenance of an effective antiviral response.
145 11289799 These include mutational escape, latency, masking of antibody-binding sites on the viral envelope, downmodulation of the class I major histocompatibility complex (MHC-I), and upregulation of the Fas ligand on the surface of infected cells.
146 11292315 This assay may therefore permit characterization of the role of MDC in HIV-1/SIV pathogenesis, and in vaccine-induced immune responses.
147 11429125 The conserved, immunogenic CD4 binding site on the viral envelope is an attractive HIV or SIV vaccine candidate.
148 11555138 Vaccination with rMVA-J5 performed at week 0, 12, and 24 induced a moderate proliferative response to whole SIV, a detectable humoral response to all but Nef SIV antigens, and failed to induce neutralizing antibodies.
149 11581386 The ability to monitor vaccine-elicited CD8(+) cytotoxic T-lymphocyte (CTL) responses in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys has been limited by our knowledge of viral epitopes predictably presented to those lymphocytes by common rhesus monkey MHC class I alleles.
150 11581386 We now define an SIV and SHIV Nef CTL epitope (YTSGPGIRY) that is presented to CD8(+) T lymphocytes by the common rhesus monkey MHC class I molecule Mamu-A*02.
151 11581386 All seven infected Mamu-A*02(+) monkeys evaluated demonstrated this response, and peptide-stimulated interferon gamma Elispot assays indicated that the response represents a large proportion of the entire CD8(+) T-lymphocyte SIV- or SHIV-specific immune response of these animals.
152 11676602 An enhanced and scalable process for the purification of SIV Gag-specific MHC tetramer.
153 11676602 The purified MHC alpha chain is refolded with beta-2-microglobulin and the target peptide antigen to form the class I MHC.
154 11709096 The efficacy of immunizing with a combination of simian immunodeficiency virus (SIV) Nef vaccines was evaluated.
155 11709096 Four vaccinates received three intradermal immunizations with recombinant vaccinia virus that expressed SIV Nef, followed by three intramuscular immunizations with rDNA also expressing SIV Nef.
156 11709096 Finally, the four vaccinates received two subcutaneous boosts with recombinant SIV Nef protein.
157 11709096 The efficacy of immunizing with a combination of simian immunodeficiency virus (SIV) Nef vaccines was evaluated.
158 11709096 Four vaccinates received three intradermal immunizations with recombinant vaccinia virus that expressed SIV Nef, followed by three intramuscular immunizations with rDNA also expressing SIV Nef.
159 11709096 Finally, the four vaccinates received two subcutaneous boosts with recombinant SIV Nef protein.
160 11709096 The efficacy of immunizing with a combination of simian immunodeficiency virus (SIV) Nef vaccines was evaluated.
161 11709096 Four vaccinates received three intradermal immunizations with recombinant vaccinia virus that expressed SIV Nef, followed by three intramuscular immunizations with rDNA also expressing SIV Nef.
162 11709096 Finally, the four vaccinates received two subcutaneous boosts with recombinant SIV Nef protein.
163 11739541 Potentiation of simian immunodeficiency virus (SIV)-specific CD4(+) and CD8(+) T cell responses by a DNA-SIV and NYVAC-SIV prime/boost regimen.
164 11739541 Therefore, an effective vaccine against HIV-1 should be able to elicit high frequencies of virus-specific CD8(+) and CD4(+) T cells.
165 11739541 The highly attenuated poxvirus-based vaccine candidate, NYVAC-SIV-gag-pol-env (NYVAC-SIV-gpe), has been shown to induce and/or expand SIV-specific CD4(+) and CD8(+) T cell responses in both naive and infected macaques.
166 11739541 Potentiation of simian immunodeficiency virus (SIV)-specific CD4(+) and CD8(+) T cell responses by a DNA-SIV and NYVAC-SIV prime/boost regimen.
167 11739541 Therefore, an effective vaccine against HIV-1 should be able to elicit high frequencies of virus-specific CD8(+) and CD4(+) T cells.
168 11739541 The highly attenuated poxvirus-based vaccine candidate, NYVAC-SIV-gag-pol-env (NYVAC-SIV-gpe), has been shown to induce and/or expand SIV-specific CD4(+) and CD8(+) T cell responses in both naive and infected macaques.
169 11943227 IL-4 increases Simian immunodeficiency virus replication despite enhanced SIV immune responses in infected rhesus macaques.
170 11943227 It is widely believed that a Th1 type CD4 response is critical for enhancement of CD8 immunity and for controlling HIV-1 infection.
171 11943227 Accordingly, the simian immunodeficiency virus (SIV) infected rhesus macaque model was used to investigate the impact of immunisation with SIV expressing DNA constructs and co-injection with IL-4 on the SIV specific immunological responses, lymphocyte cell counts, as well as the impact on viral load.
172 11943227 IL-4 is a Th2 type cytokine, which enhances antibody production and inhibits a CD4 Th1 phenotype.
173 11943227 Importantly, vaccination in the absence of IL-4 protected CD4 levels without increasing viral load.
174 11943227 IL-4 increases Simian immunodeficiency virus replication despite enhanced SIV immune responses in infected rhesus macaques.
175 11943227 It is widely believed that a Th1 type CD4 response is critical for enhancement of CD8 immunity and for controlling HIV-1 infection.
176 11943227 Accordingly, the simian immunodeficiency virus (SIV) infected rhesus macaque model was used to investigate the impact of immunisation with SIV expressing DNA constructs and co-injection with IL-4 on the SIV specific immunological responses, lymphocyte cell counts, as well as the impact on viral load.
177 11943227 IL-4 is a Th2 type cytokine, which enhances antibody production and inhibits a CD4 Th1 phenotype.
178 11943227 Importantly, vaccination in the absence of IL-4 protected CD4 levels without increasing viral load.
179 11983247 We used intracellular cytokine staining (ICS) of peripheral blood mononuclear cells (PBMCs) from animals during the acute phase of viral infection stimulated with peptides spanning the entire protein sequence of SIV to determine which peptides were recognized by CD8 and CD4 positive T cells.
180 12021334 We found that the resistance of macaque 359 to SIV infection was not due to a high level of CD8(+) suppressor activity but to an inherent resistance of its CD4(+) T cells.
181 12021334 To elucidate the basis for the unusually strong resistance of macaque 359 to SIV infection in vivo and in vitro, we investigated early events of viral infection and replication in CD4(+) cells of macaque 359, including expression and mutation screening of SIV coreceptors and analysis of viral entry and reverse transcription.
182 12021334 PCR analysis revealed a significant delay in production of early in vitro reverse transcription intermediates in macaque 359 cells compared to susceptible controls, but cell fusion assays showed that SIV entered the CD4(+) CCR5(+) cells of macaque 359 as readily as cells of macaques susceptible to SIV infection.
183 12021334 Our results suggest that the resistance of macaque 359 to SIV infection is due to a postentry block in viral replication and implicate a cellular inhibitory mechanism in its CD4(+) T cells.
184 12021334 We found that the resistance of macaque 359 to SIV infection was not due to a high level of CD8(+) suppressor activity but to an inherent resistance of its CD4(+) T cells.
185 12021334 To elucidate the basis for the unusually strong resistance of macaque 359 to SIV infection in vivo and in vitro, we investigated early events of viral infection and replication in CD4(+) cells of macaque 359, including expression and mutation screening of SIV coreceptors and analysis of viral entry and reverse transcription.
186 12021334 PCR analysis revealed a significant delay in production of early in vitro reverse transcription intermediates in macaque 359 cells compared to susceptible controls, but cell fusion assays showed that SIV entered the CD4(+) CCR5(+) cells of macaque 359 as readily as cells of macaques susceptible to SIV infection.
187 12021334 Our results suggest that the resistance of macaque 359 to SIV infection is due to a postentry block in viral replication and implicate a cellular inhibitory mechanism in its CD4(+) T cells.
188 12021334 We found that the resistance of macaque 359 to SIV infection was not due to a high level of CD8(+) suppressor activity but to an inherent resistance of its CD4(+) T cells.
189 12021334 To elucidate the basis for the unusually strong resistance of macaque 359 to SIV infection in vivo and in vitro, we investigated early events of viral infection and replication in CD4(+) cells of macaque 359, including expression and mutation screening of SIV coreceptors and analysis of viral entry and reverse transcription.
190 12021334 PCR analysis revealed a significant delay in production of early in vitro reverse transcription intermediates in macaque 359 cells compared to susceptible controls, but cell fusion assays showed that SIV entered the CD4(+) CCR5(+) cells of macaque 359 as readily as cells of macaques susceptible to SIV infection.
191 12021334 Our results suggest that the resistance of macaque 359 to SIV infection is due to a postentry block in viral replication and implicate a cellular inhibitory mechanism in its CD4(+) T cells.
192 12021334 We found that the resistance of macaque 359 to SIV infection was not due to a high level of CD8(+) suppressor activity but to an inherent resistance of its CD4(+) T cells.
193 12021334 To elucidate the basis for the unusually strong resistance of macaque 359 to SIV infection in vivo and in vitro, we investigated early events of viral infection and replication in CD4(+) cells of macaque 359, including expression and mutation screening of SIV coreceptors and analysis of viral entry and reverse transcription.
194 12021334 PCR analysis revealed a significant delay in production of early in vitro reverse transcription intermediates in macaque 359 cells compared to susceptible controls, but cell fusion assays showed that SIV entered the CD4(+) CCR5(+) cells of macaque 359 as readily as cells of macaques susceptible to SIV infection.
195 12021334 Our results suggest that the resistance of macaque 359 to SIV infection is due to a postentry block in viral replication and implicate a cellular inhibitory mechanism in its CD4(+) T cells.
196 12057610 To study whether SIV VLPs represent effective mucosal immunogens, we immunized groups of mice with VLPs alone or VLPs plus the mucosal adjuvant cholera toxin (CT) by the intranasal (i.n.) route.
197 12057610 High levels of serum IgG antibody production were achieved in mice immunized intranasally with SIV VLPs, and the antibody response was found to be antigen dose-dependent.
198 12057610 The IgG1 and IgG2a ratio indicates that immune responses induced by SIV VLPs are Th1 oriented.
199 12057610 Moreover, increased numbers of MHC I-restricted peptide-specific IFN-gamma and IL-4 producing T cells were detected in both splenocytes and lymph nodes by intranasal immunization of SIV VLP plus CT.
200 12057610 To study whether SIV VLPs represent effective mucosal immunogens, we immunized groups of mice with VLPs alone or VLPs plus the mucosal adjuvant cholera toxin (CT) by the intranasal (i.n.) route.
201 12057610 High levels of serum IgG antibody production were achieved in mice immunized intranasally with SIV VLPs, and the antibody response was found to be antigen dose-dependent.
202 12057610 The IgG1 and IgG2a ratio indicates that immune responses induced by SIV VLPs are Th1 oriented.
203 12057610 Moreover, increased numbers of MHC I-restricted peptide-specific IFN-gamma and IL-4 producing T cells were detected in both splenocytes and lymph nodes by intranasal immunization of SIV VLP plus CT.
204 12057610 To study whether SIV VLPs represent effective mucosal immunogens, we immunized groups of mice with VLPs alone or VLPs plus the mucosal adjuvant cholera toxin (CT) by the intranasal (i.n.) route.
205 12057610 High levels of serum IgG antibody production were achieved in mice immunized intranasally with SIV VLPs, and the antibody response was found to be antigen dose-dependent.
206 12057610 The IgG1 and IgG2a ratio indicates that immune responses induced by SIV VLPs are Th1 oriented.
207 12057610 Moreover, increased numbers of MHC I-restricted peptide-specific IFN-gamma and IL-4 producing T cells were detected in both splenocytes and lymph nodes by intranasal immunization of SIV VLP plus CT.
208 12390544 Protection by SIV VLP DNA prime/protein boost following mucosal SIV challenge is markedly enhanced by IL-12/GM-CSF co-administration.
209 12390544 Thus, groups of monkeys were administered three consecutive doses of pVecB7 a plasmid expressing VLP with or without plasmids expressing IL-12 and GM-CSF at weeks 0, 13 and 26.
210 12390544 While all immunized monkeys showed a marked reduction of acute viral peaks, reduction of viral load set points was only achieved in groups whose prime-boost immunizations were supplemented with IL-12/GM-CSF (prime) and/or with IL-12 (boost).
211 12390544 In summary, use of IL-12 and/or GM-CSF was shown to provide significant differences in the outcome of SIV challenge of prime/boost immunized monkeys.
212 12391187 Containment of simian immunodeficiency virus infection in vaccinated macaques: correlation with the magnitude of virus-specific pre- and postchallenge CD4+ and CD8+ T cell responses.
213 12391187 The control of viremia in these macaques was long lasting and inversely correlated to the level of both pre- and postchallenge Gag-specific lymphoproliferative responses, as well as to the level of total SIV-specific CD4(+) T lymphocyte responses at the peak of acute viremia as detected by intracellular cytokine-staining assay.
214 12396605 Responses to SIV Nef were assessed in 16 macaques also immunized with Ad5hr-SIVnef.
215 12477432 Co-immunization of rhesus macaques with plasmid vectors expressing IFN-gamma, GM-CSF, and SIV antigens enhances anti-viral humoral immunity but does not affect viremia after challenge with highly pathogenic virus.
216 12477432 To investigate the adjuvant capacity of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN-gamma), we cloned these rhesus cytokines into a mammalian expression vector.
217 12477432 Two groups of six rhesus macaques (Macaca mulatta) received intradermal immunizations of plasmid DNA coding for SIV Eng and Gag, and influenza virus nucleoprotein (Flu-NP), with or without the co-administration of plasmid DNA coding for these cytokines.
218 12477432 Co-immunization of rhesus macaques with plasmid vectors expressing IFN-gamma, GM-CSF, and SIV antigens enhances anti-viral humoral immunity but does not affect viremia after challenge with highly pathogenic virus.
219 12477432 To investigate the adjuvant capacity of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN-gamma), we cloned these rhesus cytokines into a mammalian expression vector.
220 12477432 Two groups of six rhesus macaques (Macaca mulatta) received intradermal immunizations of plasmid DNA coding for SIV Eng and Gag, and influenza virus nucleoprotein (Flu-NP), with or without the co-administration of plasmid DNA coding for these cytokines.
221 12490410 Similarly, both vaccines elicited comparable lymphoproliferative responses (LPRs) to the SIV p27 Gag and gp120 Env proteins.
222 12502820 The vaccine was composed of recombinant human immunodeficiency virus type 1 (HIV-1) gp120, NefTat fusion protein, and simian immunodeficiency virus (SIV) Nef formulated in the clinically tested adjuvant AS02A.
223 12519209 SIV-specific immune responses, including IgG and IgA binding antibodies in sera and mucosal secretions, IgG and IgA secreting cells in peripheral blood, IgG neutralizing antibodies, T-cell proliferative responses, and interferon-gamma secretion by peripheral blood mononuclear cells, were evaluated pre- and post-surgery in macaques immunized with adenovirus-SIV recombinant vaccines and SIV envelope protein and in SIV-infected macaques.
224 12710504 The cervicovaginal mucosa contains a complete set of immune cells, including antigen-presenting cells, CD4+ and CD8+ T cells, and B cells.
225 12710504 HIV/SIV-specific CD8+ cytotoxic T lymphocytes are present in the cervicovaginal mucosa of infected women and rhesus macaques.
226 12885879 Macaques primed with all three recombinants displayed significant down-modulation in numbers of gamma interferon (IFN-gamma)-secreting cells specific for SIV Nef, and the Env- and Gag-specific responses were also diminished.
227 12885879 Down-modulation was seen only during the period of Ad5hr-recombinant priming, not during subunit boosting, although SIV-specific IFN-gamma-secreting cells persisted.
228 12885879 Macaques primed with all three recombinants displayed significant down-modulation in numbers of gamma interferon (IFN-gamma)-secreting cells specific for SIV Nef, and the Env- and Gag-specific responses were also diminished.
229 12885879 Down-modulation was seen only during the period of Ad5hr-recombinant priming, not during subunit boosting, although SIV-specific IFN-gamma-secreting cells persisted.
230 12919752 Active proteins such as GFP, CAT, and SIV p27 were expressed within infected cells.
231 12969547 Use of interleukin 15 to enhance interferon-gamma production by antigen-specific stimulated lymphocytes from rhesus macaques.
232 12969547 Interleukin (IL)-15 has been demonstrated to stimulate expansion of human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) and to regulate homeostatic proliferation of CD8+ memory cells.
233 12969547 We evaluated the in vitro effect of IL-15 to increase the detection of interferon-gamma (IFN-gamma) production by antigen-specific stimulated lymphocytes from a group of rhesus macaques exposed to simian-human immunodeficiency virus (SHIV) and a second group infected with SIVmac251, before and after antiretroviral treatment (ART).
234 12969547 Results from these studies demonstrate that the presence of IL-15 during stimulation in a peptide-based ELISPOT assay greatly enhanced IFN-gamma production in both SHIV and simian immunodeficiency virus (SIV)-infected macaques.
235 12969547 IFN-gamma production was mainly mediated by CD8 lymphocytes.
236 12969547 The optimal concentrations of IL-15 that give enhancement of IFN-gamma production to specific antigen, without a significant increase in the spontaneous IFN-gamma release, ranged from 0.5 to 2.5 ng/ml.
237 12969547 Similarly, in SIV-infected macaques, IL-15 increased the mean number of IFN-gamma spots 2.7-fold in response to both SIV gag and env peptide pools.
238 14501788 Presentation of exogenous whole inactivated simian immunodeficiency virus by mature dendritic cells induces CD4+ and CD8+ T-cell responses.
239 14501788 AT-2 SIV interacts authentically with T cells and DCs and thus allows assessment of natural SIV-specific responses.
240 14501788 CD4+ and CD8+ T cells from blood or lymph nodes of SIV-infected macaques released interferon-gamma (IFN gamma) and proliferated in response to a variety of AT-2 SIV isolates.
241 14501788 Presentation of Ags derived from AT-2 SIV by DCs was more potent than presentation by comparably Ag-loaded monocytes.
242 14501788 Interestingly, SIV-pulsed mature DCs stimulated both CD4+ and CD8+ T-cell responses, whereas immature DCs primarily stimulated CD4+ T cells.
243 14694116 The long-term challenge outcome in vaccinated monkeys was correlated with the relative balance between SIV-specific IFN-gamma T-cell responses and nonspecific IFN-gamma-driven inflammation.
244 14694116 In contrast, both high tissue IFN-gamma mRNA levels and strong in vitro SIV-specific IFN-gamma T-cell responses were detected in lymphoid tissues of vaccinated-unprotected monkeys.
245 14694116 In addition, in lymphoid tissues of vaccinated-unprotected and unvaccinated monkeys, the increased IFN-gamma mRNA levels were associated with increased Mig/CXCL9, IP-10/CXCL10, and CXCR3 mRNA levels, suggesting that increased Mig/CXCL9 and IP-10/CXCL10 expression resulted in recruitment of CXCR3(+) activated T cells.
246 14694116 The long-term challenge outcome in vaccinated monkeys was correlated with the relative balance between SIV-specific IFN-gamma T-cell responses and nonspecific IFN-gamma-driven inflammation.
247 14694116 In contrast, both high tissue IFN-gamma mRNA levels and strong in vitro SIV-specific IFN-gamma T-cell responses were detected in lymphoid tissues of vaccinated-unprotected monkeys.
248 14694116 In addition, in lymphoid tissues of vaccinated-unprotected and unvaccinated monkeys, the increased IFN-gamma mRNA levels were associated with increased Mig/CXCL9, IP-10/CXCL10, and CXCR3 mRNA levels, suggesting that increased Mig/CXCL9 and IP-10/CXCL10 expression resulted in recruitment of CXCR3(+) activated T cells.
249 14722263 The core enhancer and promoter sequences of the SIV macaque 239nefstop strain (NF-kappaB/Sp1 region from -114 bp to mRNA start) have been exchanged for those of the human cytomegalovirus immediate-early promoter (CMV-IE; from -525 bp to mRNA start).
250 14741150 Avipox-based simian immunodeficiency virus (SIV) vaccines elicit a high frequency of SIV-specific CD4+ and CD8+ T-cell responses in vaccinia-experienced SIVmac251-infected macaques.
251 14741150 The ability of ALVAC- or fowlpox-based simian immunodeficiency virus (SIV) vaccines to boost SIV-specific CD4+ and CD8+ T-cell responses was tested in 10 vaccinia-experienced macaques infected with SIVmac251.
252 14741150 The overall CD8+ T-cell response to Gag was assessed using a peptide pool encompassing the entire Gag protein followed by measurement of TNF-alpha production in ICS assay.
253 14741150 Similarly, virus-specific CD4+ T-cell responses were measured by ICS for TNF-alpha following stimulation with the Gag-overlapping peptide and by proliferative response following stimulation with purified p27 Gag.
254 14741150 The two vaccine modalities effectively boosted both CD4+ and CD8+ SIV-specific T-cell response despite prior exposure to the vaccinia-derivative NYVAC vector, suggesting that sequential boosting with either avipox-based vector vaccine candidate is a realistic approach in immune therapy of human immunodeficiency virus type 1 (HIV-1)-infected individuals.
255 14741150 Avipox-based simian immunodeficiency virus (SIV) vaccines elicit a high frequency of SIV-specific CD4+ and CD8+ T-cell responses in vaccinia-experienced SIVmac251-infected macaques.
256 14741150 The ability of ALVAC- or fowlpox-based simian immunodeficiency virus (SIV) vaccines to boost SIV-specific CD4+ and CD8+ T-cell responses was tested in 10 vaccinia-experienced macaques infected with SIVmac251.
257 14741150 The overall CD8+ T-cell response to Gag was assessed using a peptide pool encompassing the entire Gag protein followed by measurement of TNF-alpha production in ICS assay.
258 14741150 Similarly, virus-specific CD4+ T-cell responses were measured by ICS for TNF-alpha following stimulation with the Gag-overlapping peptide and by proliferative response following stimulation with purified p27 Gag.
259 14741150 The two vaccine modalities effectively boosted both CD4+ and CD8+ SIV-specific T-cell response despite prior exposure to the vaccinia-derivative NYVAC vector, suggesting that sequential boosting with either avipox-based vector vaccine candidate is a realistic approach in immune therapy of human immunodeficiency virus type 1 (HIV-1)-infected individuals.
260 14741150 Avipox-based simian immunodeficiency virus (SIV) vaccines elicit a high frequency of SIV-specific CD4+ and CD8+ T-cell responses in vaccinia-experienced SIVmac251-infected macaques.
261 14741150 The ability of ALVAC- or fowlpox-based simian immunodeficiency virus (SIV) vaccines to boost SIV-specific CD4+ and CD8+ T-cell responses was tested in 10 vaccinia-experienced macaques infected with SIVmac251.
262 14741150 The overall CD8+ T-cell response to Gag was assessed using a peptide pool encompassing the entire Gag protein followed by measurement of TNF-alpha production in ICS assay.
263 14741150 Similarly, virus-specific CD4+ T-cell responses were measured by ICS for TNF-alpha following stimulation with the Gag-overlapping peptide and by proliferative response following stimulation with purified p27 Gag.
264 14741150 The two vaccine modalities effectively boosted both CD4+ and CD8+ SIV-specific T-cell response despite prior exposure to the vaccinia-derivative NYVAC vector, suggesting that sequential boosting with either avipox-based vector vaccine candidate is a realistic approach in immune therapy of human immunodeficiency virus type 1 (HIV-1)-infected individuals.
265 15067316 Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication.
266 15067316 In vivo blockade of CD28 and CD40 T cell costimulation pathways during acute simian immunodeficiency virus (SIV) infection of rhesus macaques was performed to assess the relative contributions of CD4+ T cells, CD8+ T cells, and Ab responses in modulating SIV replication and disease progression.
267 15067316 Transient administration of CTLA4-Ig and anti-CD40L mAb to SIV-infected rhesus macaques resulted in dramatic inhibition of the generation of both SIV-specific cellular and humoral immune responses.
268 15067316 Acute levels of proliferating CD8+ T cells were associated with early control of SIV viremia but did not predict ensuing set point viremia or survival.
269 15067316 The level of in vivo CD4+ T cell proliferation during acute SIV infection correlated with concomitant peak levels of SIV plasma viremia, whereas measures of in vivo CD4+ T cell proliferation that extended into chronic infection correlated with lower SIV viral load and increased survival.
270 15067316 These results suggest that proliferating CD4+ T cells function both as sources of virus production and as antiviral effectors and that increased levels of CD4+ T cell proliferation during SIV infections reflect antigen-driven antiviral responses rather than a compensatory homeostatic response.
271 15067316 These results highlight the interrelated actions of CD4+ and CD8+ T cell responses in vivo that modulate SIV replication and pathogenesis.
272 15067316 Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication.
273 15067316 In vivo blockade of CD28 and CD40 T cell costimulation pathways during acute simian immunodeficiency virus (SIV) infection of rhesus macaques was performed to assess the relative contributions of CD4+ T cells, CD8+ T cells, and Ab responses in modulating SIV replication and disease progression.
274 15067316 Transient administration of CTLA4-Ig and anti-CD40L mAb to SIV-infected rhesus macaques resulted in dramatic inhibition of the generation of both SIV-specific cellular and humoral immune responses.
275 15067316 Acute levels of proliferating CD8+ T cells were associated with early control of SIV viremia but did not predict ensuing set point viremia or survival.
276 15067316 The level of in vivo CD4+ T cell proliferation during acute SIV infection correlated with concomitant peak levels of SIV plasma viremia, whereas measures of in vivo CD4+ T cell proliferation that extended into chronic infection correlated with lower SIV viral load and increased survival.
277 15067316 These results suggest that proliferating CD4+ T cells function both as sources of virus production and as antiviral effectors and that increased levels of CD4+ T cell proliferation during SIV infections reflect antigen-driven antiviral responses rather than a compensatory homeostatic response.
278 15067316 These results highlight the interrelated actions of CD4+ and CD8+ T cell responses in vivo that modulate SIV replication and pathogenesis.
279 15067316 Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication.
280 15067316 In vivo blockade of CD28 and CD40 T cell costimulation pathways during acute simian immunodeficiency virus (SIV) infection of rhesus macaques was performed to assess the relative contributions of CD4+ T cells, CD8+ T cells, and Ab responses in modulating SIV replication and disease progression.
281 15067316 Transient administration of CTLA4-Ig and anti-CD40L mAb to SIV-infected rhesus macaques resulted in dramatic inhibition of the generation of both SIV-specific cellular and humoral immune responses.
282 15067316 Acute levels of proliferating CD8+ T cells were associated with early control of SIV viremia but did not predict ensuing set point viremia or survival.
283 15067316 The level of in vivo CD4+ T cell proliferation during acute SIV infection correlated with concomitant peak levels of SIV plasma viremia, whereas measures of in vivo CD4+ T cell proliferation that extended into chronic infection correlated with lower SIV viral load and increased survival.
284 15067316 These results suggest that proliferating CD4+ T cells function both as sources of virus production and as antiviral effectors and that increased levels of CD4+ T cell proliferation during SIV infections reflect antigen-driven antiviral responses rather than a compensatory homeostatic response.
285 15067316 These results highlight the interrelated actions of CD4+ and CD8+ T cell responses in vivo that modulate SIV replication and pathogenesis.
286 15067316 Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication.
287 15067316 In vivo blockade of CD28 and CD40 T cell costimulation pathways during acute simian immunodeficiency virus (SIV) infection of rhesus macaques was performed to assess the relative contributions of CD4+ T cells, CD8+ T cells, and Ab responses in modulating SIV replication and disease progression.
288 15067316 Transient administration of CTLA4-Ig and anti-CD40L mAb to SIV-infected rhesus macaques resulted in dramatic inhibition of the generation of both SIV-specific cellular and humoral immune responses.
289 15067316 Acute levels of proliferating CD8+ T cells were associated with early control of SIV viremia but did not predict ensuing set point viremia or survival.
290 15067316 The level of in vivo CD4+ T cell proliferation during acute SIV infection correlated with concomitant peak levels of SIV plasma viremia, whereas measures of in vivo CD4+ T cell proliferation that extended into chronic infection correlated with lower SIV viral load and increased survival.
291 15067316 These results suggest that proliferating CD4+ T cells function both as sources of virus production and as antiviral effectors and that increased levels of CD4+ T cell proliferation during SIV infections reflect antigen-driven antiviral responses rather than a compensatory homeostatic response.
292 15067316 These results highlight the interrelated actions of CD4+ and CD8+ T cell responses in vivo that modulate SIV replication and pathogenesis.
293 15067316 Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication.
294 15067316 In vivo blockade of CD28 and CD40 T cell costimulation pathways during acute simian immunodeficiency virus (SIV) infection of rhesus macaques was performed to assess the relative contributions of CD4+ T cells, CD8+ T cells, and Ab responses in modulating SIV replication and disease progression.
295 15067316 Transient administration of CTLA4-Ig and anti-CD40L mAb to SIV-infected rhesus macaques resulted in dramatic inhibition of the generation of both SIV-specific cellular and humoral immune responses.
296 15067316 Acute levels of proliferating CD8+ T cells were associated with early control of SIV viremia but did not predict ensuing set point viremia or survival.
297 15067316 The level of in vivo CD4+ T cell proliferation during acute SIV infection correlated with concomitant peak levels of SIV plasma viremia, whereas measures of in vivo CD4+ T cell proliferation that extended into chronic infection correlated with lower SIV viral load and increased survival.
298 15067316 These results suggest that proliferating CD4+ T cells function both as sources of virus production and as antiviral effectors and that increased levels of CD4+ T cell proliferation during SIV infections reflect antigen-driven antiviral responses rather than a compensatory homeostatic response.
299 15067316 These results highlight the interrelated actions of CD4+ and CD8+ T cell responses in vivo that modulate SIV replication and pathogenesis.
300 15067316 Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication.
301 15067316 In vivo blockade of CD28 and CD40 T cell costimulation pathways during acute simian immunodeficiency virus (SIV) infection of rhesus macaques was performed to assess the relative contributions of CD4+ T cells, CD8+ T cells, and Ab responses in modulating SIV replication and disease progression.
302 15067316 Transient administration of CTLA4-Ig and anti-CD40L mAb to SIV-infected rhesus macaques resulted in dramatic inhibition of the generation of both SIV-specific cellular and humoral immune responses.
303 15067316 Acute levels of proliferating CD8+ T cells were associated with early control of SIV viremia but did not predict ensuing set point viremia or survival.
304 15067316 The level of in vivo CD4+ T cell proliferation during acute SIV infection correlated with concomitant peak levels of SIV plasma viremia, whereas measures of in vivo CD4+ T cell proliferation that extended into chronic infection correlated with lower SIV viral load and increased survival.
305 15067316 These results suggest that proliferating CD4+ T cells function both as sources of virus production and as antiviral effectors and that increased levels of CD4+ T cell proliferation during SIV infections reflect antigen-driven antiviral responses rather than a compensatory homeostatic response.
306 15067316 These results highlight the interrelated actions of CD4+ and CD8+ T cell responses in vivo that modulate SIV replication and pathogenesis.
307 15067316 Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication.
308 15067316 In vivo blockade of CD28 and CD40 T cell costimulation pathways during acute simian immunodeficiency virus (SIV) infection of rhesus macaques was performed to assess the relative contributions of CD4+ T cells, CD8+ T cells, and Ab responses in modulating SIV replication and disease progression.
309 15067316 Transient administration of CTLA4-Ig and anti-CD40L mAb to SIV-infected rhesus macaques resulted in dramatic inhibition of the generation of both SIV-specific cellular and humoral immune responses.
310 15067316 Acute levels of proliferating CD8+ T cells were associated with early control of SIV viremia but did not predict ensuing set point viremia or survival.
311 15067316 The level of in vivo CD4+ T cell proliferation during acute SIV infection correlated with concomitant peak levels of SIV plasma viremia, whereas measures of in vivo CD4+ T cell proliferation that extended into chronic infection correlated with lower SIV viral load and increased survival.
312 15067316 These results suggest that proliferating CD4+ T cells function both as sources of virus production and as antiviral effectors and that increased levels of CD4+ T cell proliferation during SIV infections reflect antigen-driven antiviral responses rather than a compensatory homeostatic response.
313 15067316 These results highlight the interrelated actions of CD4+ and CD8+ T cell responses in vivo that modulate SIV replication and pathogenesis.
314 15218180 Analysis of SIV-specific T-cell levels by detection of SIV-specific gamma interferon (IFN-gamma) production revealed that these two macaques maintained SIV-specific CD8(+) T cells, even after loss of control, but lost SIV-specific CD4(+) T cells when plasma viral loads increased.
315 15218180 The remaining macaque kept viral loads at low levels and maintained SIV-specific CD4(+) T cells, as well as CD8(+) T cells, for more than 3 years.
316 15218180 Additional analysis using macaques vaccinated with a Gag-expressing Sendai virus vector also found loss of viraemia control, with loss of SIV-specific CD4(+) T cells in the chronic phase of SIV infection.
317 15218180 Thus, SIV-specific CD4(+) T cells that were able to produce IFN-gamma in response to SIV antigens were preserved by the vaccine-based partial control of primary SIV replication, but were lost with abrogation of control in the chronic phase.
318 15218180 Analysis of SIV-specific T-cell levels by detection of SIV-specific gamma interferon (IFN-gamma) production revealed that these two macaques maintained SIV-specific CD8(+) T cells, even after loss of control, but lost SIV-specific CD4(+) T cells when plasma viral loads increased.
319 15218180 The remaining macaque kept viral loads at low levels and maintained SIV-specific CD4(+) T cells, as well as CD8(+) T cells, for more than 3 years.
320 15218180 Additional analysis using macaques vaccinated with a Gag-expressing Sendai virus vector also found loss of viraemia control, with loss of SIV-specific CD4(+) T cells in the chronic phase of SIV infection.
321 15218180 Thus, SIV-specific CD4(+) T cells that were able to produce IFN-gamma in response to SIV antigens were preserved by the vaccine-based partial control of primary SIV replication, but were lost with abrogation of control in the chronic phase.
322 15218180 Analysis of SIV-specific T-cell levels by detection of SIV-specific gamma interferon (IFN-gamma) production revealed that these two macaques maintained SIV-specific CD8(+) T cells, even after loss of control, but lost SIV-specific CD4(+) T cells when plasma viral loads increased.
323 15218180 The remaining macaque kept viral loads at low levels and maintained SIV-specific CD4(+) T cells, as well as CD8(+) T cells, for more than 3 years.
324 15218180 Additional analysis using macaques vaccinated with a Gag-expressing Sendai virus vector also found loss of viraemia control, with loss of SIV-specific CD4(+) T cells in the chronic phase of SIV infection.
325 15218180 Thus, SIV-specific CD4(+) T cells that were able to produce IFN-gamma in response to SIV antigens were preserved by the vaccine-based partial control of primary SIV replication, but were lost with abrogation of control in the chronic phase.
326 15218180 Analysis of SIV-specific T-cell levels by detection of SIV-specific gamma interferon (IFN-gamma) production revealed that these two macaques maintained SIV-specific CD8(+) T cells, even after loss of control, but lost SIV-specific CD4(+) T cells when plasma viral loads increased.
327 15218180 The remaining macaque kept viral loads at low levels and maintained SIV-specific CD4(+) T cells, as well as CD8(+) T cells, for more than 3 years.
328 15218180 Additional analysis using macaques vaccinated with a Gag-expressing Sendai virus vector also found loss of viraemia control, with loss of SIV-specific CD4(+) T cells in the chronic phase of SIV infection.
329 15218180 Thus, SIV-specific CD4(+) T cells that were able to produce IFN-gamma in response to SIV antigens were preserved by the vaccine-based partial control of primary SIV replication, but were lost with abrogation of control in the chronic phase.
330 15265893 There are two principle subsets of dendritic cells (DCs); CD11c(+)CD123(-) myeloid DCs (MDCs) and CD11c(-)CD123(+) plasmacytoid DCs (PDCs).
331 15265893 Using lineage (Lin) markers to exclude non-DCs, Lin(-)HLA-DR(+)CD11c(+)CD123(-) MDCs and Lin(-)HLA-DR(+)CD11c(-)CD123(+) PDCs were identified in the blood of uninfected macaques and healthy macaques infected with SIV or simian-human immunodeficiency virus.
332 15265893 Overnight culture of DC-enriched Lin-depleted cells increased CD80 and CD86 expression.
333 15265893 IL-12 production and CD80/CD86 expression by MDC/PDC mixtures was further enhanced by CD40L and ISS-ODN treatment.
334 15265893 A CpG-B ISS-ODN increased CD80/CD86 expression by PDCs, but resulted in little IFN-alpha secretion unless IL-3 was added.
335 15265893 In contrast, a CpG-C ISS-ODN and aldrithiol-2-inactivated (AT-2) SIV induced considerable PDC activation and IFN-alpha release without needing exogenous IL-3.
336 15265893 The CpG-C ISS-ODN also stimulated IL-12 release (unlike AT-2 SIV) and augmented DC immunostimulatory activity, increasing SIV-specific T cell IFN-gamma production induced by AT-2 SIV-presenting MDC/PDC-enriched mixtures.
337 15265893 These data highlight the functional capacities of MDCs and PDCs in naive as well as healthy, infected macaques, revealing a promising CpG-C ISS-ODN-driven DC activation strategy that boosts immune function to augment preventative and therapeutic vaccine efficacy.
338 15297611 By using small-molecule competitors specific for CCR5 and CXCR4 in ex vivo assays, we found that highly pathogenic SHIV(DH12R) exclusively uses CXCR4 for infection of rhesus peripheral blood mononuclear cells, whereas SIV(mac239) and SIV(smE543) use CCR5 for entry into the same cells.
339 15297611 During the period of peak virus production in SHIV(DH12R)- or SHIV(89.6P)-infected rhesus monkeys, massive elimination of CXCR4(+) naïve CD4(+) T cells occurred.
340 15297611 In contrast, circulating CCR5(+) memory CD4(+) T cells were selectively depleted in rapidly progressing SIV-infected monkeys.
341 15356916 We targeted the SIV CCR5 coreceptor in a combined CCR5-SIV antigen immunization strategy.
342 15381725 Two groups have shown that, as in macaques infected with simian immunodeficiency virus (SIV), intestinal CD4(+) T cells are selectively and rapidly depleted in the intestine of HIV-infected patients.
343 15470050 As a result, these two molecules account for virtually all known MHC class I-restricted SIV-derived CD8+ T cell epitopes.
344 15470050 The synthesis of five Mamu-A*02 tetramers demonstrated the discrepancy between tetramer binding and IFN-gamma secretion by SIV-specific CD8+ T cells during chronic SIV infection.
345 15470050 As a result, these two molecules account for virtually all known MHC class I-restricted SIV-derived CD8+ T cell epitopes.
346 15470050 The synthesis of five Mamu-A*02 tetramers demonstrated the discrepancy between tetramer binding and IFN-gamma secretion by SIV-specific CD8+ T cells during chronic SIV infection.
347 15518803 Use of a Clostridium perfringens vector to express high levels of SIV p27 protein for the development of an oral SIV vaccine.
348 15518803 Here we report the construction of a recombinant C. perfringens vaccine vector expressing high levels of SIV p27 during sporulation.
349 15518803 Furthermore, dendritic cells (DCs) beneath the mucosal surface in the PPs were able to capture SIV p27 antigen, when PPs were exposed to C. perfringens expressing SIV p27 antigen.
350 15518803 Use of a Clostridium perfringens vector to express high levels of SIV p27 protein for the development of an oral SIV vaccine.
351 15518803 Here we report the construction of a recombinant C. perfringens vaccine vector expressing high levels of SIV p27 during sporulation.
352 15518803 Furthermore, dendritic cells (DCs) beneath the mucosal surface in the PPs were able to capture SIV p27 antigen, when PPs were exposed to C. perfringens expressing SIV p27 antigen.
353 15518803 Use of a Clostridium perfringens vector to express high levels of SIV p27 protein for the development of an oral SIV vaccine.
354 15518803 Here we report the construction of a recombinant C. perfringens vaccine vector expressing high levels of SIV p27 during sporulation.
355 15518803 Furthermore, dendritic cells (DCs) beneath the mucosal surface in the PPs were able to capture SIV p27 antigen, when PPs were exposed to C. perfringens expressing SIV p27 antigen.
356 15699118 Contrasting effects of low-dose IL-2 on vaccine-boosted simian immunodeficiency virus (SIV)-specific CD4+ and CD8+ T cells in macaques chronically infected with SIVmac251.
357 15699118 In this study, we investigated how continuous low-dose IL-2 affected the CD4+ and CD8+ T cell response induced by two inoculations of a canarypox recombinant SIV-based vaccine candidate in healthy macaques chronically infected with SIVmac251.
358 15699118 Vaccination in the presence of IL-2 significantly augmented Gag-specific CD8+ T cell responses, but actually reduced Gag-specific CD4+ T cell responses.
359 15699118 Although IL-2 at low doses did not change the overall concentration of circulating CD4+ or CD8+ T cells, it expanded the frequency of CD4+CD25+ T cells.
360 15699118 Depletion of the CD4+CD25+ T cells in vitro, however, did not result in a reconstitution of Gag-specific CD4+ responses or augmentation of SIV-specific CD8+ T cell responses.
361 15699118 Thus, we conclude that the decrease in virus-specific CD4+ T cell response may be due to IL-2-promoted redistribution of cells from the circulation, or due to Ag-induced cell death, rather than suppression by a T regulatory population.
362 15721357 Decreased levels of plasma viremia in vaccinated animals were evident as early as 7 days post-challenge, well before the expansion of SIV-specific CD8+ T cells.
363 15721357 Expansion of SIV-specific CD8+ T cells was not observed in peripheral blood or tissues until at least 14 days after infection and did not occur in most animals until after the initial peak of viral replication.
364 15721357 The observation that expansion of SIV-specific CD8+ T cells is delayed until 7 days or more after initial detection of viremia highlights fundamental limitations in the ability of lentivirus-specific CD8+ T cells to mediate protection against challenge.
365 15721357 Decreased levels of plasma viremia in vaccinated animals were evident as early as 7 days post-challenge, well before the expansion of SIV-specific CD8+ T cells.
366 15721357 Expansion of SIV-specific CD8+ T cells was not observed in peripheral blood or tissues until at least 14 days after infection and did not occur in most animals until after the initial peak of viral replication.
367 15721357 The observation that expansion of SIV-specific CD8+ T cells is delayed until 7 days or more after initial detection of viremia highlights fundamental limitations in the ability of lentivirus-specific CD8+ T cells to mediate protection against challenge.
368 15721357 Decreased levels of plasma viremia in vaccinated animals were evident as early as 7 days post-challenge, well before the expansion of SIV-specific CD8+ T cells.
369 15721357 Expansion of SIV-specific CD8+ T cells was not observed in peripheral blood or tissues until at least 14 days after infection and did not occur in most animals until after the initial peak of viral replication.
370 15721357 The observation that expansion of SIV-specific CD8+ T cells is delayed until 7 days or more after initial detection of viremia highlights fundamental limitations in the ability of lentivirus-specific CD8+ T cells to mediate protection against challenge.
371 15919908 It has been shown previously that the nonstructural protein NS1 of influenza virus is an alpha/beta interferon (IFN-alpha/beta) antagonist, both in vitro and in experimental animal model systems.
372 15919908 Here we investigated the role of the NS1 protein in the virulence of a swine influenza virus (SIV) isolate in pigs by using reverse genetics.
373 15919908 Growth properties of TX/98 viruses with mutated NS1, induction of IFN in tissue culture, and virulence-attenuation in pigs were analyzed and compared to those of the recombinant wild-type TX/98 virus.
374 15919908 Our results indicate that deletions in the NS1 protein decrease the ability of the TX/98 virus to prevent IFN-alpha/beta synthesis in pig cells.
375 15919908 Moreover, all NS1 mutant viruses were attenuated in pigs, and this correlated with the amount of IFN-alpha/beta induced in vitro.
376 15919908 These data suggest that the NS1 protein of SIV is a virulence factor.
377 15919908 Due to their attenuation, NS1-mutated swine influenza viruses might have a great potential as live attenuated vaccine candidates against SIV infections of pigs.
378 15919908 It has been shown previously that the nonstructural protein NS1 of influenza virus is an alpha/beta interferon (IFN-alpha/beta) antagonist, both in vitro and in experimental animal model systems.
379 15919908 Here we investigated the role of the NS1 protein in the virulence of a swine influenza virus (SIV) isolate in pigs by using reverse genetics.
380 15919908 Growth properties of TX/98 viruses with mutated NS1, induction of IFN in tissue culture, and virulence-attenuation in pigs were analyzed and compared to those of the recombinant wild-type TX/98 virus.
381 15919908 Our results indicate that deletions in the NS1 protein decrease the ability of the TX/98 virus to prevent IFN-alpha/beta synthesis in pig cells.
382 15919908 Moreover, all NS1 mutant viruses were attenuated in pigs, and this correlated with the amount of IFN-alpha/beta induced in vitro.
383 15919908 These data suggest that the NS1 protein of SIV is a virulence factor.
384 15919908 Due to their attenuation, NS1-mutated swine influenza viruses might have a great potential as live attenuated vaccine candidates against SIV infections of pigs.
385 15919908 It has been shown previously that the nonstructural protein NS1 of influenza virus is an alpha/beta interferon (IFN-alpha/beta) antagonist, both in vitro and in experimental animal model systems.
386 15919908 Here we investigated the role of the NS1 protein in the virulence of a swine influenza virus (SIV) isolate in pigs by using reverse genetics.
387 15919908 Growth properties of TX/98 viruses with mutated NS1, induction of IFN in tissue culture, and virulence-attenuation in pigs were analyzed and compared to those of the recombinant wild-type TX/98 virus.
388 15919908 Our results indicate that deletions in the NS1 protein decrease the ability of the TX/98 virus to prevent IFN-alpha/beta synthesis in pig cells.
389 15919908 Moreover, all NS1 mutant viruses were attenuated in pigs, and this correlated with the amount of IFN-alpha/beta induced in vitro.
390 15919908 These data suggest that the NS1 protein of SIV is a virulence factor.
391 15919908 Due to their attenuation, NS1-mutated swine influenza viruses might have a great potential as live attenuated vaccine candidates against SIV infections of pigs.
392 15956558 Interestingly, at the time of challenge, animals expressing the Mamu-A*01 major histocompatibility complex class I allele showed significantly higher frequencies of SIV-specific CD8+ T-cell responses and lower neutralizing antibody titers than those in Mamu-A*01- animals.
393 16061983 In addition to CD4 and co-receptors (most often used CCR5 and CXCR6 by SIV), GHOST(3) cells have been engineered to express the green fluorescent protein following virus infection.
394 16128921 SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques.
395 16128921 The cDNA for macaque IL-12 and CD40L were cloned into DNA vectors.
396 16128921 Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL-12 or CD40L.
397 16128921 The IL-12 expanded antigen-specific IFN-gamma positive effector cells as well as granzyme B production.
398 16128921 The vaccine immune responses contained both a CD8 component as well a CD4 component.
399 16128921 The adjuvanted DNA vaccines illustrate that IL-12 enhances a CD8 vaccine immune response, however, different cellular profiles.
400 16274888 Immunization with SIV DNA vaccine alone induced SIV-specific IFN-gamma ELISPOT responses in only two of four vaccinated macaques, whereas all animals developed SIV-specific T-cell responses and Env- and Tat-specific antibody responses following the rAd/SIV vaccine boost.
401 16288822 Cellular immune responses, monitored by SIV gag-specific IFN-gamma ELISpot assay, were also significantly higher (p=0.007, 0.019) when the pDNA vaccine was co-immunized with IL-12 pDNA at high and low doses.
402 16386958 Intradermal (i.d.) inoculation of guinea pigs with 0.1 mg of rBCG-SIVGag resulted in the induction of delayed-type hypersensitivity (DTH) responses to both purified protein derivative (PPD) of tuberculin and SIV Gag p27 protein; responses that were maintained for the duration of the 50-week study.
403 16386958 In contrast, guinea pigs orally vaccinated with 160 mg of the same antigen exhibited a long-lasting DTH response to the SIV Gag p27 protein, but mounted no response to PPD.
404 16386958 Proliferative responses to SIV Gag p27 and PPD antigens were detected in both i.d. and orally immunized animals; however, the levels of PPD-specific responses were significantly higher in guinea pigs immunized by the i.d. than the oral route.
405 16386958 A significant increase in the level of PPD- and SIV Gag p27-specific IFNgamma mRNA expression was also detected in both immunization groups receiving rBCG-SIVGag.
406 16386958 In addition, both i.d. and oral immunization with rBCG-SIVGag induced PPD- and SIV Gag p27-specific serum IgG responses.
407 16386958 Intradermal (i.d.) inoculation of guinea pigs with 0.1 mg of rBCG-SIVGag resulted in the induction of delayed-type hypersensitivity (DTH) responses to both purified protein derivative (PPD) of tuberculin and SIV Gag p27 protein; responses that were maintained for the duration of the 50-week study.
408 16386958 In contrast, guinea pigs orally vaccinated with 160 mg of the same antigen exhibited a long-lasting DTH response to the SIV Gag p27 protein, but mounted no response to PPD.
409 16386958 Proliferative responses to SIV Gag p27 and PPD antigens were detected in both i.d. and orally immunized animals; however, the levels of PPD-specific responses were significantly higher in guinea pigs immunized by the i.d. than the oral route.
410 16386958 A significant increase in the level of PPD- and SIV Gag p27-specific IFNgamma mRNA expression was also detected in both immunization groups receiving rBCG-SIVGag.
411 16386958 In addition, both i.d. and oral immunization with rBCG-SIVGag induced PPD- and SIV Gag p27-specific serum IgG responses.
412 16386958 Intradermal (i.d.) inoculation of guinea pigs with 0.1 mg of rBCG-SIVGag resulted in the induction of delayed-type hypersensitivity (DTH) responses to both purified protein derivative (PPD) of tuberculin and SIV Gag p27 protein; responses that were maintained for the duration of the 50-week study.
413 16386958 In contrast, guinea pigs orally vaccinated with 160 mg of the same antigen exhibited a long-lasting DTH response to the SIV Gag p27 protein, but mounted no response to PPD.
414 16386958 Proliferative responses to SIV Gag p27 and PPD antigens were detected in both i.d. and orally immunized animals; however, the levels of PPD-specific responses were significantly higher in guinea pigs immunized by the i.d. than the oral route.
415 16386958 A significant increase in the level of PPD- and SIV Gag p27-specific IFNgamma mRNA expression was also detected in both immunization groups receiving rBCG-SIVGag.
416 16386958 In addition, both i.d. and oral immunization with rBCG-SIVGag induced PPD- and SIV Gag p27-specific serum IgG responses.
417 16386958 Intradermal (i.d.) inoculation of guinea pigs with 0.1 mg of rBCG-SIVGag resulted in the induction of delayed-type hypersensitivity (DTH) responses to both purified protein derivative (PPD) of tuberculin and SIV Gag p27 protein; responses that were maintained for the duration of the 50-week study.
418 16386958 In contrast, guinea pigs orally vaccinated with 160 mg of the same antigen exhibited a long-lasting DTH response to the SIV Gag p27 protein, but mounted no response to PPD.
419 16386958 Proliferative responses to SIV Gag p27 and PPD antigens were detected in both i.d. and orally immunized animals; however, the levels of PPD-specific responses were significantly higher in guinea pigs immunized by the i.d. than the oral route.
420 16386958 A significant increase in the level of PPD- and SIV Gag p27-specific IFNgamma mRNA expression was also detected in both immunization groups receiving rBCG-SIVGag.
421 16386958 In addition, both i.d. and oral immunization with rBCG-SIVGag induced PPD- and SIV Gag p27-specific serum IgG responses.
422 16386958 Intradermal (i.d.) inoculation of guinea pigs with 0.1 mg of rBCG-SIVGag resulted in the induction of delayed-type hypersensitivity (DTH) responses to both purified protein derivative (PPD) of tuberculin and SIV Gag p27 protein; responses that were maintained for the duration of the 50-week study.
423 16386958 In contrast, guinea pigs orally vaccinated with 160 mg of the same antigen exhibited a long-lasting DTH response to the SIV Gag p27 protein, but mounted no response to PPD.
424 16386958 Proliferative responses to SIV Gag p27 and PPD antigens were detected in both i.d. and orally immunized animals; however, the levels of PPD-specific responses were significantly higher in guinea pigs immunized by the i.d. than the oral route.
425 16386958 A significant increase in the level of PPD- and SIV Gag p27-specific IFNgamma mRNA expression was also detected in both immunization groups receiving rBCG-SIVGag.
426 16386958 In addition, both i.d. and oral immunization with rBCG-SIVGag induced PPD- and SIV Gag p27-specific serum IgG responses.
427 16522814 We found that while SIV-specific T-cell responses are detectable in the majority of animals, their magnitude and breadth are, in fact, lower than what has been described in HIV-infected humans, both in terms of cytokine production (ie, IFN-gamma, TNF-alpha, and IL-2) and degranulation (ie, CD107a expression).
428 16672547 Using the SIV-macaque system to advance oral vaccine research, we examined macaque PDC and MDC biology, identifying ways to activate DCs and boost antiviral immunity.
429 16672547 Immunostimulatory oligodeoxyribonucleotides (ISS-ODNs) stimulated PDC/MDC mixtures to up-regulate co-stimulatory molecule expression and to secrete both IFN-alpha and IL-12.
430 16672547 Additionally, ISS-ODNs augmented SIV-specific IFN-gamma responses induced by virus-bearing DCs.
431 16691294 IL-15 induces CD4 effector memory T cell production and tissue emigration in nonhuman primates.
432 16691294 Here, we demonstrate that IL-15 dramatically increases in vivo proliferation of rhesus macaque (RM) CD4+ and CD8+ T EM cells with little effect on the naive or central memory T (T CM) cell subsets, a response pattern that is quite distinct from that of either IL-2 or IL-7.
433 16691294 In RMs with uncontrolled SIV infection and highly activated immune systems, IL-15 did not significantly increase CD4+ T EM cell proliferation, but with virologic control and concomitant reduction in immune activation by ART, IL-15 responsiveness was again observed.
434 16691294 These data suggest that therapeutic use of IL-15 in the setting of ART might facilitate specific restoration of the CD4 + T cell compartment that is the primary target of HIV with less risk of exhausting precursor T cell compartments or generating potentially deleterious regulatory subsets.
435 16896154 CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques.
436 16896154 Regulatory T (T(reg)) cells are a subset of CD25(+)CD4(+) T cells that constitutively express high levels of cytotoxic T lymphocyte antigen-4 (CTLA-4) and suppress T-cell activation and effector functions.
437 16896154 CTLA-4 blockade decreased expression of the tryptophan-depleting enzyme IDO and the level of the suppressive cytokine transforming growth factor-beta (TGF-beta) in tissues.
438 16896154 CTLA-4 blockade was associated with decreased viral RNA levels in lymph nodes and an increase in the effector function of both SIV-specific CD4(+) and CD8(+) T cells.
439 16904153 A DNA prime-oral Listeria boost vaccine in rhesus macaques induces a SIV-specific CD8 T cell mucosal response characterized by high levels of alpha4beta7 integrin and an effector memory phenotype.
440 16904153 In this study in Rhesus macaques, we tested whether IL-12 or IL-15 in a DNA prime-oral Listeria boost amplifies the SIV-Gag-specific CD8 mucosal response.
441 16904153 SIV-specific CD8 T cells were demonstrated in the peripheral blood (PB) in all test vaccine groups, but not the control group.
442 16904153 Neither Il-12 nor IL-15 amplified the frequency of SIV-specific CD8 T cells in the gut.
443 16904153 A DNA prime-oral Listeria boost vaccine in rhesus macaques induces a SIV-specific CD8 T cell mucosal response characterized by high levels of alpha4beta7 integrin and an effector memory phenotype.
444 16904153 In this study in Rhesus macaques, we tested whether IL-12 or IL-15 in a DNA prime-oral Listeria boost amplifies the SIV-Gag-specific CD8 mucosal response.
445 16904153 SIV-specific CD8 T cells were demonstrated in the peripheral blood (PB) in all test vaccine groups, but not the control group.
446 16904153 Neither Il-12 nor IL-15 amplified the frequency of SIV-specific CD8 T cells in the gut.
447 16934309 Decreased number of CD4+ and CD8+ T cells that express the interleukin-7 receptor in blood and tissues of SIV-infected macaques.
448 16934309 In HIV/SIV infection, IL-7 expression is increased, likely to compensate for T cell loss, suggesting that supraphysiological administration of IL-7 could provide additional benefit.
449 16934309 However, the ability of T cells to respond to IL-7 is dependent on the level of expression of the IL-7 receptor (IL-7R) in T cells in various body compartments.
450 16934309 In here, we investigated the proportion of IL-7R(+) T cells in blood, spleen, gut, and genitourinary tract of healthy and SIV-infected macaques with various degrees of CD4(+) T cell depletion.
451 16934309 We found that the percentage of T cells expressing IL-7R was significantly lower in both CD4(+) and CD8(+) T cell subsets in SIV-infected macaques than in healthy animals and this decrease directly correlated with the CD4(+) T cell number.
452 16934309 Importantly, the proportion of CD4(+) and CD8(+) T cells expressing IL-7R in blood paralleled that found in tissues.
453 16934309 IL-7R(+) T cells within the SIV-specific CD8(+) T cells varied and were lowest in most tissues of viremic macaques, likely reflecting continuous antigen stimulation of effector cells.
454 16939702 The hemagglutination inhibition (HI) titer of the sham-inoculated group (n = 12) showed continued antibody decay whereas piglets vaccinated with Ad-5 SIV (n = 23) developed an active immune response by the second week post-vaccination.
455 16939702 At 4 weeks-of-age when the HI titer of the sham-inoculated group had decayed to 45, the sham-inoculated group and half of the Ad-5 SIV vaccinated pigs were boosted with a commercial inactivated SIV vaccine.
456 16939702 These recombinant Ad-5 SIV vaccines are useful for priming the immune system to override the effects of maternally derived antibodies which interfere with conventional SIV vaccines.
457 16939702 The hemagglutination inhibition (HI) titer of the sham-inoculated group (n = 12) showed continued antibody decay whereas piglets vaccinated with Ad-5 SIV (n = 23) developed an active immune response by the second week post-vaccination.
458 16939702 At 4 weeks-of-age when the HI titer of the sham-inoculated group had decayed to 45, the sham-inoculated group and half of the Ad-5 SIV vaccinated pigs were boosted with a commercial inactivated SIV vaccine.
459 16939702 These recombinant Ad-5 SIV vaccines are useful for priming the immune system to override the effects of maternally derived antibodies which interfere with conventional SIV vaccines.
460 16939702 The hemagglutination inhibition (HI) titer of the sham-inoculated group (n = 12) showed continued antibody decay whereas piglets vaccinated with Ad-5 SIV (n = 23) developed an active immune response by the second week post-vaccination.
461 16939702 At 4 weeks-of-age when the HI titer of the sham-inoculated group had decayed to 45, the sham-inoculated group and half of the Ad-5 SIV vaccinated pigs were boosted with a commercial inactivated SIV vaccine.
462 16939702 These recombinant Ad-5 SIV vaccines are useful for priming the immune system to override the effects of maternally derived antibodies which interfere with conventional SIV vaccines.
463 16943292 We have recently shown that survival in plasmid DNA-primed/recombinant adenovirus-boosted rhesus monkeys that are challenged with the simian immunodeficiency virus SIVmac251 is associated with the preservation postchallenge of central memory CD4(+) T lymphocytes and robust gamma interferon (IFN-gamma)-producing SIV-specific CD8(+) and CD4(+) T-lymphocyte responses.
464 16943292 We show that the preservation of the SIV-specific central memory CD8(+) T-lymphocyte population and a linked SIV-specific CD4(+) T-lymphocyte response are associated with prolonged survival in vaccinated monkeys following challenge.
465 16943292 Furthermore, we demonstrate that SIV-specific IFN-gamma-, tumor necrosis factor alpha-, and interleukin-2-producing T lymphocytes are all comparably associated with protection against disease progression.
466 16943292 We have recently shown that survival in plasmid DNA-primed/recombinant adenovirus-boosted rhesus monkeys that are challenged with the simian immunodeficiency virus SIVmac251 is associated with the preservation postchallenge of central memory CD4(+) T lymphocytes and robust gamma interferon (IFN-gamma)-producing SIV-specific CD8(+) and CD4(+) T-lymphocyte responses.
467 16943292 We show that the preservation of the SIV-specific central memory CD8(+) T-lymphocyte population and a linked SIV-specific CD4(+) T-lymphocyte response are associated with prolonged survival in vaccinated monkeys following challenge.
468 16943292 Furthermore, we demonstrate that SIV-specific IFN-gamma-, tumor necrosis factor alpha-, and interleukin-2-producing T lymphocytes are all comparably associated with protection against disease progression.
469 16943292 We have recently shown that survival in plasmid DNA-primed/recombinant adenovirus-boosted rhesus monkeys that are challenged with the simian immunodeficiency virus SIVmac251 is associated with the preservation postchallenge of central memory CD4(+) T lymphocytes and robust gamma interferon (IFN-gamma)-producing SIV-specific CD8(+) and CD4(+) T-lymphocyte responses.
470 16943292 We show that the preservation of the SIV-specific central memory CD8(+) T-lymphocyte population and a linked SIV-specific CD4(+) T-lymphocyte response are associated with prolonged survival in vaccinated monkeys following challenge.
471 16943292 Furthermore, we demonstrate that SIV-specific IFN-gamma-, tumor necrosis factor alpha-, and interleukin-2-producing T lymphocytes are all comparably associated with protection against disease progression.
472 17050602 SIV Gag-specific CD4 and CD8 T-cell responses were induced by sequential DNA/FPV vaccination, although lower FPV doses, VV/FPV vaccination, and DNA vaccines alone were not as consistently immunogenic.
473 17108046 Incorporation of glycosylphosphatidylinositol-anchored granulocyte- macrophage colony-stimulating factor or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles.
474 17108046 To accomplish this we generated chimeric simian immunodeficiency virus (SIV) VLPs containing either glycosylphosphatidylinositol (GPI)-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity and ability to enhance immune responses in vivo.
475 17108046 Immunization of mice with chimeric SIV VLPs containing GM-CSF induced SIV Env-specific antibodies as well as neutralizing activity at significantly higher levels than those induced by standard SIV VLPs, SIV VLPs containing CD40L, or standard VLPs mixed with soluble GM-CSF.
476 17108046 In addition, mice immunized with chimeric SIV VLPs containing either GM-CSF or CD40L showed significantly increased CD4(+)- and CD8(+)-T-cell responses to SIV Env, compared to standard SIV VLPs.
477 17108046 We propose that anchoring immunostimulatory molecules into SIV VLPs can be a promising approach to augmenting the efficacy of VLP antigens.
478 17108046 Incorporation of glycosylphosphatidylinositol-anchored granulocyte- macrophage colony-stimulating factor or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles.
479 17108046 To accomplish this we generated chimeric simian immunodeficiency virus (SIV) VLPs containing either glycosylphosphatidylinositol (GPI)-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity and ability to enhance immune responses in vivo.
480 17108046 Immunization of mice with chimeric SIV VLPs containing GM-CSF induced SIV Env-specific antibodies as well as neutralizing activity at significantly higher levels than those induced by standard SIV VLPs, SIV VLPs containing CD40L, or standard VLPs mixed with soluble GM-CSF.
481 17108046 In addition, mice immunized with chimeric SIV VLPs containing either GM-CSF or CD40L showed significantly increased CD4(+)- and CD8(+)-T-cell responses to SIV Env, compared to standard SIV VLPs.
482 17108046 We propose that anchoring immunostimulatory molecules into SIV VLPs can be a promising approach to augmenting the efficacy of VLP antigens.
483 17108046 Incorporation of glycosylphosphatidylinositol-anchored granulocyte- macrophage colony-stimulating factor or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles.
484 17108046 To accomplish this we generated chimeric simian immunodeficiency virus (SIV) VLPs containing either glycosylphosphatidylinositol (GPI)-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity and ability to enhance immune responses in vivo.
485 17108046 Immunization of mice with chimeric SIV VLPs containing GM-CSF induced SIV Env-specific antibodies as well as neutralizing activity at significantly higher levels than those induced by standard SIV VLPs, SIV VLPs containing CD40L, or standard VLPs mixed with soluble GM-CSF.
486 17108046 In addition, mice immunized with chimeric SIV VLPs containing either GM-CSF or CD40L showed significantly increased CD4(+)- and CD8(+)-T-cell responses to SIV Env, compared to standard SIV VLPs.
487 17108046 We propose that anchoring immunostimulatory molecules into SIV VLPs can be a promising approach to augmenting the efficacy of VLP antigens.
488 17108046 Incorporation of glycosylphosphatidylinositol-anchored granulocyte- macrophage colony-stimulating factor or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles.
489 17108046 To accomplish this we generated chimeric simian immunodeficiency virus (SIV) VLPs containing either glycosylphosphatidylinositol (GPI)-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity and ability to enhance immune responses in vivo.
490 17108046 Immunization of mice with chimeric SIV VLPs containing GM-CSF induced SIV Env-specific antibodies as well as neutralizing activity at significantly higher levels than those induced by standard SIV VLPs, SIV VLPs containing CD40L, or standard VLPs mixed with soluble GM-CSF.
491 17108046 In addition, mice immunized with chimeric SIV VLPs containing either GM-CSF or CD40L showed significantly increased CD4(+)- and CD8(+)-T-cell responses to SIV Env, compared to standard SIV VLPs.
492 17108046 We propose that anchoring immunostimulatory molecules into SIV VLPs can be a promising approach to augmenting the efficacy of VLP antigens.
493 17142751 We have shown that the CpG-C ISS-ODN C274 stimulates macaque blood dendritic cells (DCs) and B cells and augments SIV-specific IFN-gamma responses in vitro.
494 17142751 This was particularly apparent at the level of CD80 (less so CD86) expression by CD123(+) plasmacytoid DCs and was further boosted in the presence of additional C274 in vitro.
495 17142751 This was more pronounced when cells were exposed to additional stimuli in vitro, producing IFN-alpha, IL-3, IL-6, IL-12, TNF-alpha, CCL2, CCL3, CCL5, and CXCL8.
496 17142751 Elevated IFN-alpha, CCL2, and CCL5 were also detected in the plasma after C274 injection.
497 17166912 In conclusion, we demonstrated that the transduction of DCs in vitro with pseudotyped single-cycle SIVs expressing IFN-gamma increased DC activation and augmented T-cell priming activity.
498 17179668 Moreover, intradermal administration of rDIsSIV gag/pol or of MVA/SIV239 gag/pol elicited similar levels of IFN-gamma spot-forming cells specific for SIV Gag.
499 17237418 The strongest correlates of preserved CD4(+) T cell counts were a low percentage of circulating effector T cells (CD28(-)CD95(+) and/or IL-7R/CD127(-)) and a high percentage of CD4(+)CD25(+) T cells.
500 17237418 The absence of AIDS in these "CD4(low)" naturally SIV-infected SMs defines a protective role of the reduced immune activation even in the context of a significant CD4(+) T cell depletion.
501 17346134 To determine if the anti-HIV-1 Gag(p55) immune interference was specific to HIV-1 Env(gp120), mice were co-immunized with plasmids expressing the surface envelope protein from two additional lentiviruses, Env(gp130)-SIV or Env(gp90)-EIAV, or a soluble form of hemagglutinin (sHA) from influenza virus and HIV-1 Gag(p55)- or SIV Gag(p55)-DNA.
502 17376899 Following infection, the majority (>95%) of Gag-specific CD8 T cells expressed PD-1, and the level of PD-1 expression per cell increased over time.
503 17376899 In vitro blockade of PD-1 resulted in enhanced proliferation of SIV-specific CD8 as well as CD4 T cells.
504 17376899 In contrast, following vaccination, the majority of peak effector Gag-specific CD8 T cells expressed low levels of PD-1, and these levels decreased further as the cells differentiated into memory cells.
505 17376899 In addition, following SHIV challenge of these vaccinated macaques, the level of PD-1 expression on Gag-specific CD8 T cells correlated positively with plasma viremia.
506 17376899 These results demonstrate that SIV-specific CD8 T cells express PD-1 after exposure to antigen but downregulate expression under conditions of antigen clearance and enhance expression under conditions of antigen persistence.
507 17376899 They also demonstrate that the level of PD-1 expression per cell rather than the presence or absence of expression plays an important role in regulating CD8 T-cell dysfunction in pathogenic SIV infection.
508 17440051 SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection.
509 17440051 Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion.
510 17440051 Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells.
511 17440051 The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested.
512 17440051 PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression.
513 17440051 SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation.
514 17440051 While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells.
515 17440051 PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation.
516 17440051 Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death.
517 17440051 Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection.
518 17440051 SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection.
519 17440051 Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion.
520 17440051 Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells.
521 17440051 The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested.
522 17440051 PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression.
523 17440051 SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation.
524 17440051 While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells.
525 17440051 PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation.
526 17440051 Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death.
527 17440051 Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection.
528 17440051 SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection.
529 17440051 Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion.
530 17440051 Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells.
531 17440051 The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested.
532 17440051 PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression.
533 17440051 SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation.
534 17440051 While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells.
535 17440051 PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation.
536 17440051 Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death.
537 17440051 Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection.
538 17440051 SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection.
539 17440051 Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion.
540 17440051 Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells.
541 17440051 The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested.
542 17440051 PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression.
543 17440051 SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation.
544 17440051 While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells.
545 17440051 PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation.
546 17440051 Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death.
547 17440051 Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection.
548 17440051 SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection.
549 17440051 Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion.
550 17440051 Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells.
551 17440051 The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested.
552 17440051 PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression.
553 17440051 SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation.
554 17440051 While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells.
555 17440051 PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation.
556 17440051 Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death.
557 17440051 Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection.
558 17499328 Boosting of DermaVir-primed serum antibody levels was noted following gp140(SHIV89.6P)/p27(SIV) immunization.
559 17641886 Molecular typing of major histocompatibility complex class I alleles in the Indian rhesus macaque which restrict SIV CD8+ T cell epitopes.
560 17989178 Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression.
561 17989178 These elite controllers (ECs) mounted a broad SIV-specific CD4(+) T-cell response.
562 17989178 Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control.
563 17989178 Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression.
564 17989178 These elite controllers (ECs) mounted a broad SIV-specific CD4(+) T-cell response.
565 17989178 Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control.
566 17989178 Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression.
567 17989178 These elite controllers (ECs) mounted a broad SIV-specific CD4(+) T-cell response.
568 17989178 Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control.
569 18068748 Efficient inhibition of SIV replication in rhesus CD4+ T-cell clones by autologous immortalized SIV-specific CD8+ T-cell clones.
570 18068748 We investigated the capacity of SIV-specific CTL clones (effectors), immortalized by transduction with human telomerase reverse transcriptase (hTERT), to suppress SIV replication in autologous hTERT immortalized CD4(+) T-cell clones (targets).
571 18068748 Our in vitro assays of inhibition of viral replication, using T-cell clones as effectors and targets, provide a well-defined approach for evaluating possible mechanisms of CTL-mediated control of viral production which may involve direct killing of infected target cells and/or release of proinflammatory cytokines such as IFN-gamma and TNF-alpha.
572 18097036 IL-15 treatment during acute simian immunodeficiency virus (SIV) infection increases viral set point and accelerates disease progression despite the induction of stronger SIV-specific CD8+ T cell responses.
573 18097036 Although IL-15 induced a 2- to 3-fold increase in SIV-specific CD8+ T cell and NK cell numbers at peak viremia and reduced lymph node (LN) SIV-infected cells, this had no impact on peak viremia and did not lower viral set point.
574 18097036 At viral set point, however, activated SIV-specific CD8+ T cells and NK cells were reduced in the blood of IL-15-treated animals and LN SIV-infected cells were increased.
575 18097036 Week 30 LN from IL-15-treated animals had significantly increased Gag-specific CD8+ T cell numbers, whereas total cell, lymphocyte, and CD4+ T cell numbers were reduced.
576 18097036 IL-15 increased Ki-67+CD4+ T cells at week 1 of treatment and reduced blood CCR5+ and CD45RA-CD62L- CD4+ T cells.
577 18097036 The frequency of day 7 Ki-67+CD4+ T cells strongly correlated with viral set point.
578 18097036 These findings suggest that CD4+ T cell activation during acute infection determines subsequent viral set point and IL-15 treatment by increasing such activation elevates viral set point.
579 18753198 Seven rhesus macaques per group were primed twice with multigenic SIV plasmid DNA with or without interleukin-12 (IL-12) DNA or IL-15 DNA.
580 18753198 After a multigenic replicating Ad-SIV immunization, all groups received two booster immunizations with SIV gp140 and SIV Nef protein.
581 18753198 Macaques that received IL-15-DNA exhibited higher peak anti-Nef titers, a more rapid anti-Nef anamnestic response postchallenge, and expanded CD8(CM) T cells 2 weeks postchallenge compared to the DNA-only group.
582 19027133 Both immunization strategies induced strong SIV Gag-specific IFN-gamma and T-cell proliferation responses and mediated a conservation of CD4(+) memory T-cells and a reduction of viral load during peak viremia following infection.
583 19193388 Macaques co-inoculated with rIL-15 and SIV/CMVDelta vif proviral plasmids showed significantly improved SIV-specific CD8 T cell immunity characterized by increased IFN-gamma ELISPOT and polyfunctional CD8 T cell responses.
584 19219024 RhCMV vectors expressing SIV Gag, Rev-Tat-Nef and Env persistently infected rhesus macaques, regardless of preexisting RhCMV immunity, and primed and maintained robust, SIV-specific CD4+ and CD8+ TEM cell responses (characterized by coordinate tumor necrosis factor, interferon-gamma and macrophage inflammatory protein-1beta expression, cytotoxic degranulation and accumulation at extralymphoid sites) in the absence of neutralizing antibodies.
585 19439474 Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques.
586 19439474 Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins.
587 19439474 SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals.
588 19439474 Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection.
589 19439474 SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia.
590 19439474 Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques.
591 19439474 Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins.
592 19439474 SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals.
593 19439474 Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection.
594 19439474 SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia.
595 19439474 Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques.
596 19439474 Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins.
597 19439474 SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals.
598 19439474 Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection.
599 19439474 SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia.
600 19439474 Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques.
601 19439474 Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins.
602 19439474 SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals.
603 19439474 Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection.
604 19439474 SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia.
605 19741603 We compared the efficacy of an intranasal or intramuscular Simian immunodeficiency virus (SIV)+ interleukin (IL)-2+IL-15 DNA/SIV-MVA (modified vaccinia virus Ankara) vaccination in preventing disease progression in SIVmac251 intrarectally challenged rhesus macaques.
606 19741603 Regardless of vaccination status, long-term viremia control and preservation of CD4(+) C(M) T cells was detected in animals with significantly higher systemic CD8(+)/tumor necrosis factor (TNF)-alpha(+) and CD8(+)/interferon (IFN)-gamma(+) T-cell responses and higher SIV-specific CD4(+)/IL-2(+) responses in colorectal T cells.
607 19741603 We compared the efficacy of an intranasal or intramuscular Simian immunodeficiency virus (SIV)+ interleukin (IL)-2+IL-15 DNA/SIV-MVA (modified vaccinia virus Ankara) vaccination in preventing disease progression in SIVmac251 intrarectally challenged rhesus macaques.
608 19741603 Regardless of vaccination status, long-term viremia control and preservation of CD4(+) C(M) T cells was detected in animals with significantly higher systemic CD8(+)/tumor necrosis factor (TNF)-alpha(+) and CD8(+)/interferon (IFN)-gamma(+) T-cell responses and higher SIV-specific CD4(+)/IL-2(+) responses in colorectal T cells.
609 19779309 Tonsillar application of AT-2 SIV affords partial protection against rectal challenge with SIVmac239.
610 19949108 In this paper, we show that translation from an alternate reading frame of both the Rev-encoding DNA plasmid and the rAd5 vector engendered Env(788-795)RY8-specific CD8(+) T cells of greater magnitude than "normal" SIV infection.
611 20089645 Recombinant yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 gag induces SIV-specific CD8+ T-cell responses in rhesus macaques.
612 20089645 We show that recombinant attenuated yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 Gag sequences can be used as a vector to generate SIV-specific CD8(+) T-cell responses in the rhesus macaque.
613 20089645 Priming with recombinant BCG expressing SIV antigens increased the frequency of these SIV-specific CD8(+) T-cell responses after recombinant YF17D boosting.
614 20089645 These recombinant YF17D-induced SIV-specific CD8(+) T cells secreted several cytokines, were largely effector memory T cells, and suppressed viral replication in CD4(+) T cells.
615 20089645 Recombinant yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 gag induces SIV-specific CD8+ T-cell responses in rhesus macaques.
616 20089645 We show that recombinant attenuated yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 Gag sequences can be used as a vector to generate SIV-specific CD8(+) T-cell responses in the rhesus macaque.
617 20089645 Priming with recombinant BCG expressing SIV antigens increased the frequency of these SIV-specific CD8(+) T-cell responses after recombinant YF17D boosting.
618 20089645 These recombinant YF17D-induced SIV-specific CD8(+) T cells secreted several cytokines, were largely effector memory T cells, and suppressed viral replication in CD4(+) T cells.
619 20089645 Recombinant yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 gag induces SIV-specific CD8+ T-cell responses in rhesus macaques.
620 20089645 We show that recombinant attenuated yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 Gag sequences can be used as a vector to generate SIV-specific CD8(+) T-cell responses in the rhesus macaque.
621 20089645 Priming with recombinant BCG expressing SIV antigens increased the frequency of these SIV-specific CD8(+) T-cell responses after recombinant YF17D boosting.
622 20089645 These recombinant YF17D-induced SIV-specific CD8(+) T cells secreted several cytokines, were largely effector memory T cells, and suppressed viral replication in CD4(+) T cells.
623 20089645 Recombinant yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 gag induces SIV-specific CD8+ T-cell responses in rhesus macaques.
624 20089645 We show that recombinant attenuated yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 Gag sequences can be used as a vector to generate SIV-specific CD8(+) T-cell responses in the rhesus macaque.
625 20089645 Priming with recombinant BCG expressing SIV antigens increased the frequency of these SIV-specific CD8(+) T-cell responses after recombinant YF17D boosting.
626 20089645 These recombinant YF17D-induced SIV-specific CD8(+) T cells secreted several cytokines, were largely effector memory T cells, and suppressed viral replication in CD4(+) T cells.
627 20551910 Here, we performed a head-to-head evaluation of the Merck Ad5 SIV vaccine and an optimized electroporation (EP) delivered SIV DNA vaccine in macaques.
628 20551910 We observed significant differences in the quantity of IFNgamma responses by enzyme-linked immunosorbent spot (ELISpot), greater proliferative capacity of CD8(+) T cells, and increased polyfunctionality of both CD4(+) and CD8(+) T cells in the DNA-vaccinated group.
629 20618768 Following intradermal injection of recombinant DIs expressing simian immunodeficiency virus gag (rDIsSIVgag), we observed increased levels of SIV p27-specific IgA and IgG antibodies in faecal extracts and plasma samples, and antibody-forming cells in the intestinal mucosa and spleen of C57BL/6 mice.
630 20618768 Induction of Gag-specific IFN-gamma spot-forming CD8(+) T cells in the spleen, small intestinal intraepithelial lymphocytes, and submandibular lymph nodes was observed in the intradermally injected mice.
631 20702730 Emergence of simian immunodeficiency virus-specific cytotoxic CD4+ T cells and increased humoral responses correlate with control of rebounding viremia in CD8-depleted macaques infected with Rev-independent live-attenuated simian immunodeficiency virus.
632 20702730 Monitoring immune responses at the time of viral control demonstrated a burst of circulating SIV-specific CD4(+) T cells characterized as CD45RA(-)CD28(+)CD95(+)CCR7(-) and also granzyme B(+), suggesting cytotoxic ability.
633 20702730 These data demonstrate that a combination of cellular responses mediated by CD4(+) T cells and humoral responses was associated with the rapid control of the rebounding viremia in macaques infected by the Rev-independent live-attenuated SIV, even in the absence of measurable SIV-specific CD8(+) T cells in the blood, emphasizing the importance of different components of the immune response for full control of SIV infection.
634 20719708 Recent data also suggest that IL-15 acts, not only on CD8+ T cells and natural killer cells, but also on effector memory CD4+ T cells.
635 20719708 IL-15 clearly expands very different CD4+ T cell subpopulations than IL-2 in SIV-infected animals, and may be useful for the restoration of effector memory CD4+ T cells that are depleted early in HIV and SIV infection.
636 20739530 Here, we show that SIV-specific CD8+ T cells from SIV-infected rhesus macaques target 14 epitopes in eight ARFs during SIV infection.
637 20812010 Here, we analyzed anamnestic SIV-specific CD4+ T-cell responses expanding immediately after challenge and show that successful vaccinees consistently targeted a short region of the Gag-p27 Capsid (amino acids 249-291).
638 20812010 Analysis of SIV-specific CD4+ T-cell responses elicited by a successful vaccine may have important implications in the understanding of vaccine design.
639 20812010 Here, we analyzed anamnestic SIV-specific CD4+ T-cell responses expanding immediately after challenge and show that successful vaccinees consistently targeted a short region of the Gag-p27 Capsid (amino acids 249-291).
640 20812010 Analysis of SIV-specific CD4+ T-cell responses elicited by a successful vaccine may have important implications in the understanding of vaccine design.
641 20877632 A tonsillar PolyICLC/AT-2 SIV therapeutic vaccine maintains low viremia following antiretroviral therapy cessation.
642 21041730 Furthermore, the vaccine-elicited SIV Gag-specific CD4(+) and CD8(+) T lymphocyte polyfunctional cytokine responses were more robust in milk than in blood after each virus vector boost.
643 21041730 Importantly, only limited and transient increases in the proportion of activated or CCR5-expressing CD4(+) T lymphocytes in milk occurred after vaccination.
644 21076059 Preexisting immunity decreased SIV-specific CD8 and CD4 T cell responses but preserved the SIV-specific humoral immunity.
645 21076059 Factors that correlated with early colorectal viral control included 1) the presence of anti-SIV IgA in rectal secretions, 2) high-avidity binding Ab for the native form of Env, and 3) low magnitude of vaccine-elicited SIV-specific CD4 T cells displaying the CCR5 viral coreceptor.
646 21076059 The frequency of SIV-specific CD8 T cells in blood and colorectal tissue at 2 wk postchallenge did not correlate with early colorectal viral control.
647 21076059 Preexisting immunity decreased SIV-specific CD8 and CD4 T cell responses but preserved the SIV-specific humoral immunity.
648 21076059 Factors that correlated with early colorectal viral control included 1) the presence of anti-SIV IgA in rectal secretions, 2) high-avidity binding Ab for the native form of Env, and 3) low magnitude of vaccine-elicited SIV-specific CD4 T cells displaying the CCR5 viral coreceptor.
649 21076059 The frequency of SIV-specific CD8 T cells in blood and colorectal tissue at 2 wk postchallenge did not correlate with early colorectal viral control.
650 21076059 Preexisting immunity decreased SIV-specific CD8 and CD4 T cell responses but preserved the SIV-specific humoral immunity.
651 21076059 Factors that correlated with early colorectal viral control included 1) the presence of anti-SIV IgA in rectal secretions, 2) high-avidity binding Ab for the native form of Env, and 3) low magnitude of vaccine-elicited SIV-specific CD4 T cells displaying the CCR5 viral coreceptor.
652 21076059 The frequency of SIV-specific CD8 T cells in blood and colorectal tissue at 2 wk postchallenge did not correlate with early colorectal viral control.
653 21277409 Gp96 SIV Ig immunization induces potent polyepitope specific, multifunctional memory responses in rectal and vaginal mucosa.
654 21277409 Tetramer positive CD8 CTL expressed appropriate functional (granzyme B) and migration markers (CD103).
655 21277409 The polyepitope specificity of the mucosal CD8 and CD4 response is evident from a strong, multifunctional cytokine response upon stimulation with peptides covering the gag, tat and env proteins.
656 21317390 The efficacy of two SIV DNA plus recombinant modified vaccinia virus Ankara nasal vaccine regimens, one combined with plasmids expressing IL-2 and IL-15, the other with plasmids expressing GM-CSF, IL-12, and TNF-α, which may better stimulate humoral responses, was evaluated in two female rhesus macaque groups.
657 21317390 There was a statistically significant correlation between levels of CD4(+)/IFN-γ(+) and CD8(+)/IFN-γ(+) T cell percentages on the day of challenge and the control of viremia at week 60 postchallenge or survival.
658 21317390 Postchallenge immunological correlates of protection were systemic anti-SIV Gag + Env CD4(+)/IL-2(+), CD4(+)/IFN-γ(+), and CD8(+)/TNF-α(+) T cells and vaginal anti-SIV Gag + Env CD8(+) T cell total monofunctional responses.
659 21317533 Here we have demonstrated that acute, SIV-induced CD4(+) T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3(+)CD4(-)CD8(-) T cells (double-negative T cells) partially compensates for CD4(+) T cell function in these animals.
660 21317533 These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4(+) T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4(+) T cell-like helper functions upon SIV-induced CD4(+) T cell depletion in this species.
661 21317533 Here we have demonstrated that acute, SIV-induced CD4(+) T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3(+)CD4(-)CD8(-) T cells (double-negative T cells) partially compensates for CD4(+) T cell function in these animals.
662 21317533 These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4(+) T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4(+) T cell-like helper functions upon SIV-induced CD4(+) T cell depletion in this species.
663 21562493 This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors.
664 21562493 Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance.
665 21562493 This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors.
666 21562493 Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance.
667 21734035 There was no significant difference in the overall magnitude of SIV-specific antibodies or CD8 T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines.
668 21842371 This review serves to outline the various non-human primate models that can best serve to address this issue, a summary of our knowledge on the various subsets of NK cells (one of the major innate immune cell lineage) that have an impact on the course of disease, the potential pathways that regulate their function and the potential role of the KIRs on SIV-induced disease course.
669 21890164 A chimeric measles virus with a lentiviral envelope replicates exclusively in CD4+/CCR5+ cells.
670 21890164 The presence of SIV gp160 as the only envelope protein on chimeric particles surface altered the cell tropism of the new virus from CD46+ to CD4+ cells.
671 22084443 Structural basis of diverse peptide accommodation by the rhesus macaque MHC class I molecule Mamu-B*17: insights into immune protection from simian immunodeficiency virus.
672 22084443 The MHC class I molecule Mamu-B*17 has been associated with elite control of SIV infection in rhesus macaques, akin to the protective effects described for HLA-B*57 in HIV-infected individuals.
673 22084443 In this study, we determined the crystal structures of Mamu-B*17 in complex with eight different peptides corresponding to immunodominant SIV(mac)239-derived CD8(+) T cell epitopes: HW8 (HLEVQGYW), GW10 (GSHLEVQGYW), MW9 (MHPAQTSQW), QW9 (QTSQWDDPW), FW9 (FQWMGYELW), MF8 (MRHVLEPF), IW9 (IRYPKTFGW), and IW11 (IRYPKTFGWLW).
674 22156519 The Ad5 SIV vaccine induced CD8(+) T cell responses in 70% of the monkeys, which is similar to the proportion of humans that responded to the vaccine in the Step Trial.
675 22156519 Although setpoint viral loads were unaffected in Step vaccinees, the Ad5 SIV-immunized animals had significantly lower acute-phase plasma vRNA levels compared to unimmunized animals.
676 22156519 The Ad5 SIV vaccine induced CD8(+) T cell responses in 70% of the monkeys, which is similar to the proportion of humans that responded to the vaccine in the Step Trial.
677 22156519 Although setpoint viral loads were unaffected in Step vaccinees, the Ad5 SIV-immunized animals had significantly lower acute-phase plasma vRNA levels compared to unimmunized animals.
678 22441256 HIV and simian immunodeficiency virus (SIV) CD8 T cells have been of particular interest since they were demonstrated to be temporally associated with reduction in virus load shortly following transmission.
679 22441256 Here, we briefly review the phenotypic and functional properties of HIV-specific and SIV-specific CD8 T-cell subsets during HIV infection and consider the influence of viral variation with specific responses that are associated with disease progression or control.
680 22441256 HIV and simian immunodeficiency virus (SIV) CD8 T cells have been of particular interest since they were demonstrated to be temporally associated with reduction in virus load shortly following transmission.
681 22441256 Here, we briefly review the phenotypic and functional properties of HIV-specific and SIV-specific CD8 T-cell subsets during HIV infection and consider the influence of viral variation with specific responses that are associated with disease progression or control.
682 22442716 This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood.
683 22451717 CD4(+) T(N)-depleted RMs responded to SIVmac239 infection with markedly attenuated SIV-specific CD4(+) T cell responses, delayed SIVenv-specific Ab responses, and reduced SIV-specific CD8(+) T cell responses.
684 22491464 Multiple comparisons among these groups revealed significant differences in survival periods, peripheral CD4(+) T-cell decline, and SIV-specific CD4(+) T-cell polyfunctionality in the chronic phase.
685 22492918 Mamu class I and II gene products were linked together with HIV gp140, simian immunodeficiency virus (SIV) p27 and heat-shock protein 70 to dextran.
686 23260669 The tolerogenic vaccine induced MHC-Ib/E-restricted CD8(+) regulatory T cells (Tregs) that suppressed SIV-harboring CD4(+) T cell activation and ex vivo SIV replication in 15 of 16 animals without inducing SIV-specific antibodies or cytotoxic T lymphocytes.
687 23325679 Antibodies to gp120 and PD-1 expression on virus-specific CD8+ T cells in protection from simian AIDS.
688 23325679 We compared the relative efficacies against simian immunodeficiency virus (SIV) challenge of three vaccine regimens that elicited similar frequencies of SIV-specific CD4(+) and CD8(+) T-cell responses but differed in the level of antibody responses to the gp120 envelope protein.
689 23325679 Mamu-A*01 macaques of this third group exhibited persistent Gag CD8(+)CM9(+) effector memory T cells with low expression of surface Programmed death-1 (PD-1) receptor and high levels of expression of genes associated with major histocompatibility complex class I (MHC-I) and MHC-II antigen.
690 23325679 The fact that control of SIV replication was associated with both high titers of antibodies to the SIV envelope protein and durable effector SIV-specific CD8(+) T cells suggests the hypothesis that the presence of antibodies at the time of challenge may increase innate immune recruiting activity by enhancing antigen uptake and may result in improvement of the quality and potency of secondary SIV-specific CD8(+) T-cell responses.
691 23401588 Cohort 3 was injected with cells secreting gp96-Ig (no SIV Ags) vaccines.
692 23408627 A comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-SIV immunity that may be critical to protection from SIV infection and disease.
693 23408627 All four immunizations generated mucosal SIV-specific IgA.
694 23408627 Oral immunization was as effective as vaginal immunization in inducing SIV-specific IgA in vaginal secretions and generated greater IgA responses in rectal secretions and saliva samples compared to the other immunization routes.
695 23408627 Vaccination also induced CD4(+) and CD8(+) T-cell responses in the rectal and vaginal mucosa with greater functional heterogeneity than in blood samples.
696 23408627 Significantly higher CD8(+) granzyme B-positive T-cell responses were observed systemically after intestinal vaccination and in rectal cells after oral immunization.
697 23408627 The majority of SIV-specific T cells that produced granzyme B did not produce cytokines.
698 23408627 A comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-SIV immunity that may be critical to protection from SIV infection and disease.
699 23408627 All four immunizations generated mucosal SIV-specific IgA.
700 23408627 Oral immunization was as effective as vaginal immunization in inducing SIV-specific IgA in vaginal secretions and generated greater IgA responses in rectal secretions and saliva samples compared to the other immunization routes.
701 23408627 Vaccination also induced CD4(+) and CD8(+) T-cell responses in the rectal and vaginal mucosa with greater functional heterogeneity than in blood samples.
702 23408627 Significantly higher CD8(+) granzyme B-positive T-cell responses were observed systemically after intestinal vaccination and in rectal cells after oral immunization.
703 23408627 The majority of SIV-specific T cells that produced granzyme B did not produce cytokines.
704 23408627 A comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-SIV immunity that may be critical to protection from SIV infection and disease.
705 23408627 All four immunizations generated mucosal SIV-specific IgA.
706 23408627 Oral immunization was as effective as vaginal immunization in inducing SIV-specific IgA in vaginal secretions and generated greater IgA responses in rectal secretions and saliva samples compared to the other immunization routes.
707 23408627 Vaccination also induced CD4(+) and CD8(+) T-cell responses in the rectal and vaginal mucosa with greater functional heterogeneity than in blood samples.
708 23408627 Significantly higher CD8(+) granzyme B-positive T-cell responses were observed systemically after intestinal vaccination and in rectal cells after oral immunization.
709 23408627 The majority of SIV-specific T cells that produced granzyme B did not produce cytokines.
710 23408627 A comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-SIV immunity that may be critical to protection from SIV infection and disease.
711 23408627 All four immunizations generated mucosal SIV-specific IgA.
712 23408627 Oral immunization was as effective as vaginal immunization in inducing SIV-specific IgA in vaginal secretions and generated greater IgA responses in rectal secretions and saliva samples compared to the other immunization routes.
713 23408627 Vaccination also induced CD4(+) and CD8(+) T-cell responses in the rectal and vaginal mucosa with greater functional heterogeneity than in blood samples.
714 23408627 Significantly higher CD8(+) granzyme B-positive T-cell responses were observed systemically after intestinal vaccination and in rectal cells after oral immunization.
715 23408627 The majority of SIV-specific T cells that produced granzyme B did not produce cytokines.
716 23509365 After priming, RMs that received SIV Gag protein plus poly-IC developed significantly higher frequencies of SIV Gag-specific CD4(+) Th1 responses in blood and bronchoalveolar lavage (BAL) fluid lymphocytes compared with all other adjuvants, and low-level SIV Gag-specific CD8(+) T cell responses.
717 23509365 In contrast, the anamnestic SIV Gag-specific CD4(+) T cell response in BAL was enhanced by SIV Gag protein priming with poly-IC or CpG, which correlated with partial control of early viral replication after SIVmac251 challenge.
718 23509365 After priming, RMs that received SIV Gag protein plus poly-IC developed significantly higher frequencies of SIV Gag-specific CD4(+) Th1 responses in blood and bronchoalveolar lavage (BAL) fluid lymphocytes compared with all other adjuvants, and low-level SIV Gag-specific CD8(+) T cell responses.
719 23509365 In contrast, the anamnestic SIV Gag-specific CD4(+) T cell response in BAL was enhanced by SIV Gag protein priming with poly-IC or CpG, which correlated with partial control of early viral replication after SIVmac251 challenge.
720 23824823 Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity.
721 23824823 However, the cellular mechanisms that sustain PD-1(high) virus-specific CD8 T cell responses during chronic infection are unknown.
722 23824823 Here, we show that the PD-1(high) phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIV-specific CD8 T cell pool.
723 23824823 Mathematical modeling of 5-bromo-2' deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1(high) compared to PD-1(low) CD8 T cells in all memory compartments.
724 23824823 Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1(high) cells, but virtually all PD-1(low) cells, returned to rest after activation.
725 23824823 Our data suggest that the persistence of PD-1(high) SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate.
726 24153227 Our recent immune correlate study revealed that degree of protection against pathogenic SIV challenge strongly correlated with the SIV-specific CD4+ and CD8+ T cell responses in the lymph node but neither with the responses of such T cells in the peripheral blood and mucosal tissues nor with humoral immune responses.
727 24155376 The efficacy of oral, intestinal, nasal, and vaginal vaccinations with DNA simian immunodeficiency virus (SIV)/interleukin-2 (IL-2)/IL-15, SIV Gag/Pol/Env recombinant modified vaccinia virus Ankara (rMVA), and AT-2 SIVmac239 inactivated particles was compared in rhesus macaques after low-dose vaginal challenge with SIVmac251.
728 24155376 The levels of anti-SIV gamma interferon-positive, CD4(+), and CD8(+) T cells at the time of first challenge inversely correlated with viremia and directly correlated with protection from infection and longer survival.
729 24210124 High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function.
730 24210124 It transiently decreased expression of Ki67 and α4β7 in PBMC CD4(+) and CD8(+) Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels.
731 24348253 Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.
732 24348253 Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro.
733 24348253 Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers.
734 24348253 CD69 expression was increased in semen T cells by SIV infection, at all stages of infection.
735 24348253 Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1.
736 24348253 Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages).
737 24348253 Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.
738 24348253 Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro.
739 24348253 Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers.
740 24348253 CD69 expression was increased in semen T cells by SIV infection, at all stages of infection.
741 24348253 Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1.
742 24348253 Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages).
743 24348253 Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.
744 24348253 Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro.
745 24348253 Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers.
746 24348253 CD69 expression was increased in semen T cells by SIV infection, at all stages of infection.
747 24348253 Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1.
748 24348253 Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages).
749 24348253 Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.
750 24348253 Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro.
751 24348253 Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers.
752 24348253 CD69 expression was increased in semen T cells by SIV infection, at all stages of infection.
753 24348253 Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1.
754 24348253 Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages).
755 24349100 To gain insights into mechanisms of protection by LAVs that could aid development of effective vaccines to prevent HIV-1 transmission to women, we used in situ tetramer staining to determine whether increased densities or changes in the local distribution of SIV-specific CD8 T cells correlated with the maturation of SIVΔnef vaccine-induced protection prior to and after intra-vaginal challenge with wild-type SIVmac251.
756 24418046 On the host side, a synergistic effect between PRRSV and SIV co-infections was observed for some transcripts such as TLR3, RIG-I, and IFNβ in PCLS.
757 24671203 Regulation of SIV antigen-specific CD4+ T cellular immunity via autophagosome-mediated MHC II molecule-targeting antigen presentation in mice.
758 24671203 Recent studies have suggested that macroautophagy plays a crucial role in modulating adaptive immune responses toward CD4+ T cells or CD8+ T cells.
759 24729621 Whereas SIV-infected RM show selective numeric preservation of CD4(+) T(SCM), SIV infection induced a complex perturbation of these cells defined by depletion of CD4(+)CCR5(+) T(SCM), increased rates of CD4(+) T(SCM) proliferation, and high levels of direct virus infection.
760 24729621 In contrast, nonpathogenic SIV infection of SM evidenced preservation of both CD4(+) T(SCM) and CD4(+) central memory T cells, with normal levels of CD4(+) T(SCM) proliferation, and lack of selective depletion of CD4(+)CCR5(+) T(SCM).
761 24729621 Whereas SIV-infected RM show selective numeric preservation of CD4(+) T(SCM), SIV infection induced a complex perturbation of these cells defined by depletion of CD4(+)CCR5(+) T(SCM), increased rates of CD4(+) T(SCM) proliferation, and high levels of direct virus infection.
762 24729621 In contrast, nonpathogenic SIV infection of SM evidenced preservation of both CD4(+) T(SCM) and CD4(+) central memory T cells, with normal levels of CD4(+) T(SCM) proliferation, and lack of selective depletion of CD4(+)CCR5(+) T(SCM).
763 24907411 RepAd/Env vaccination induced early SIV-specific IgA in rectal secretions before Env boosting, although mucosal IgA and IgG responses were readily detected at necropsy in ALVAC/Env, RepAd/Env, DNA&Env and DNA vaccinated animals.
764 25043006 We show that blockade of the IFN-I receptor caused reduced antiviral gene expression, increased SIV reservoir size and accelerated CD4 T-cell depletion with progression to AIDS despite decreased T-cell activation.
765 25043006 However, continued IFN-α2a treatment induced IFN-I desensitization and decreased antiviral gene expression, enabling infection with increased SIV reservoir size and accelerated CD4 T-cell loss.
766 25043006 Thus, the timing of IFN-induced innate responses in acute SIV infection profoundly affects overall disease course and outweighs the detrimental consequences of increased immune activation.
767 25043006 We show that blockade of the IFN-I receptor caused reduced antiviral gene expression, increased SIV reservoir size and accelerated CD4 T-cell depletion with progression to AIDS despite decreased T-cell activation.
768 25043006 However, continued IFN-α2a treatment induced IFN-I desensitization and decreased antiviral gene expression, enabling infection with increased SIV reservoir size and accelerated CD4 T-cell loss.
769 25043006 Thus, the timing of IFN-induced innate responses in acute SIV infection profoundly affects overall disease course and outweighs the detrimental consequences of increased immune activation.
770 25043006 We show that blockade of the IFN-I receptor caused reduced antiviral gene expression, increased SIV reservoir size and accelerated CD4 T-cell depletion with progression to AIDS despite decreased T-cell activation.
771 25043006 However, continued IFN-α2a treatment induced IFN-I desensitization and decreased antiviral gene expression, enabling infection with increased SIV reservoir size and accelerated CD4 T-cell loss.
772 25043006 Thus, the timing of IFN-induced innate responses in acute SIV infection profoundly affects overall disease course and outweighs the detrimental consequences of increased immune activation.
773 25071760 Mucosal SIV Vaccines Comprising Inactivated Virus Particles and Bacterial Adjuvants Induce CD8(+) T-Regulatory Cells that Suppress SIV-Positive CD4(+) T-Cell Activation and Prevent SIV Infection in the Macaque Model.
774 25071760 In contrast to all established human and veterinary vaccines, these three vaccine regimens did not elicit SIV-specific antibodies nor cytotoxic T-lymphocytes but induced a previously unrecognized population of non-cytolytic MHCIb/E-restricted CD8(+) T-regulatory cells that suppressed the activation of SIV-positive CD4(+) T-lymphocytes.
775 25071760 Mucosal SIV Vaccines Comprising Inactivated Virus Particles and Bacterial Adjuvants Induce CD8(+) T-Regulatory Cells that Suppress SIV-Positive CD4(+) T-Cell Activation and Prevent SIV Infection in the Macaque Model.
776 25071760 In contrast to all established human and veterinary vaccines, these three vaccine regimens did not elicit SIV-specific antibodies nor cytotoxic T-lymphocytes but induced a previously unrecognized population of non-cytolytic MHCIb/E-restricted CD8(+) T-regulatory cells that suppressed the activation of SIV-positive CD4(+) T-lymphocytes.
777 25246494 The inhibitory receptor programmed death-1 (PD-1) has been shown to regulate CD8 T cell function during chronic SIV infection; however, its role on CD4 T cells, specifically in the gut-associated lymphoid tissue, is less well understood.
778 25246494 In this study, we show that a subset of CD4 T cells expresses high levels of PD-1 (PD-1(hi)) in the rectal mucosa, a preferential site of virus replication.
779 25246494 The majority of these PD-1(hi) CD4 T cells expressed Bcl-6 and CXCR5, markers characteristic of T follicular helper cells in the lymph nodes.
780 25246494 Following a pathogenic SIV infection, the frequency of PD-1(hi) cells (as a percentage of CD4 T cells) dramatically increased in the rectal mucosa; however, a significant fraction of them did not express CXCR5.
781 25246494 Interestingly, vaccinated SIV controllers did not present with this aberrant PD-1(hi) CD4 T cell enrichment, and this lack of enrichment was associated with the presence of higher frequencies of SIV-specific granzyme B(+) CD8 T cells within the lymphoid tissue, suggesting a role for antiviral CD8 T cells in limiting aberrant expansion of PD-1(hi) CD4 T cells.
782 25246494 These results highlight the importance of developing vaccines that enhance antiviral CD8 T cells at sites of preferential viral replication and support the need for developing therapeutic interventions that limit expansion of SIV(+)PD-1(hi) CD4 T cells at mucosal sites as a means to enhance viral control.
783 25348621 Expansion of dysfunctional Tim-3-expressing effector memory CD8+ T cells during simian immunodeficiency virus infection in rhesus macaques.
784 25348621 The T cell Ig- and mucin domain-containing molecule-3 (Tim-3) negative immune checkpoint receptor demarcates functionally exhausted CD8(+) T cells arising from chronic stimulation in viral infections like HIV.
785 25348621 Tim-3 blockade leads to improved antiviral CD8(+) T cell responses in vitro and, therefore, represents a novel intervention strategy to restore T cell function in vivo and protect from disease progression.
786 25348621 We report that Tim-3(+)CD8(+) T cell frequencies are significantly increased in lymph nodes, but not in peripheral blood, in SIV-infected animals.
787 25348621 Tim-3(+)PD-1(+)CD8(+) T cells are similarly increased during SIV infection and positively correlate with SIV plasma viremia.
788 25348621 Tim-3 expression was found primarily on effector memory CD8(+) T cells in all tissues examined.
789 25348621 Tim-3(+)CD8(+) T cells have lower Ki-67 content and minimal cytokine responses to SIV compared with Tim-3(-)CD8(+) T cells.
790 25348621 During acute-phase SIV replication, Tim-3 expression peaked on SIV-specific CD8(+) T cells by 2 wk postinfection and then rapidly diminished, irrespective of mutational escape of cognate Ag, suggesting non-TCR-driven mechanisms for Tim-3 expression.
791 25348621 Thus, rhesus Tim-3 in SIV infection partially mimics human Tim-3 in HIV infection and may serve as a novel model for targeted studies focused on rejuvenating HIV-specific CD8(+) T cell responses.
792 25348621 Expansion of dysfunctional Tim-3-expressing effector memory CD8+ T cells during simian immunodeficiency virus infection in rhesus macaques.
793 25348621 The T cell Ig- and mucin domain-containing molecule-3 (Tim-3) negative immune checkpoint receptor demarcates functionally exhausted CD8(+) T cells arising from chronic stimulation in viral infections like HIV.
794 25348621 Tim-3 blockade leads to improved antiviral CD8(+) T cell responses in vitro and, therefore, represents a novel intervention strategy to restore T cell function in vivo and protect from disease progression.
795 25348621 We report that Tim-3(+)CD8(+) T cell frequencies are significantly increased in lymph nodes, but not in peripheral blood, in SIV-infected animals.
796 25348621 Tim-3(+)PD-1(+)CD8(+) T cells are similarly increased during SIV infection and positively correlate with SIV plasma viremia.
797 25348621 Tim-3 expression was found primarily on effector memory CD8(+) T cells in all tissues examined.
798 25348621 Tim-3(+)CD8(+) T cells have lower Ki-67 content and minimal cytokine responses to SIV compared with Tim-3(-)CD8(+) T cells.
799 25348621 During acute-phase SIV replication, Tim-3 expression peaked on SIV-specific CD8(+) T cells by 2 wk postinfection and then rapidly diminished, irrespective of mutational escape of cognate Ag, suggesting non-TCR-driven mechanisms for Tim-3 expression.
800 25348621 Thus, rhesus Tim-3 in SIV infection partially mimics human Tim-3 in HIV infection and may serve as a novel model for targeted studies focused on rejuvenating HIV-specific CD8(+) T cell responses.
801 25356757 In rhesus macaques (RMs), experimental depletion of CD4+ T-cells prior to SIV infection results in higher viremia and emergence of CD4-independent SIV-envelopes.
802 25768938 Transcription factor expression patterns in SIV-specific CD8+ T cells in SIVΔnef-vaccinated animals were distinct from those observed in purified CD8+ T cell subsets obtained from naïve animals, and were intermediate to expression profiles of purified central memory and effector memory T cells.
803 25768938 Expression of transcription factors associated with effector differentiation, such as ID2 and RUNX3, were decreased over time, while expression of transcription factors associated with quiescence or memory differentiation, such as TCF7, BCOR and EOMES, increased.
804 25768938 CD8+ T cells specific for a more conserved epitope expressed higher levels of TBX21 and BATF, and appeared more effector-like than cells specific for an escaped epitope, consistent with continued activation by replicating vaccine virus.
805 25844718 Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects.
806 25844718 Furthermore, evaluation of overlapping SIV p24 peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9.
807 25844718 Intracellular staining analysis for cytotoxins and phenotyping for CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic T lymphocyte-associated molecules including perforin, granzyme B, granzyme A, and/or expression of CD107a.
808 25844718 Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects.
809 25844718 Furthermore, evaluation of overlapping SIV p24 peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9.
810 25844718 Intracellular staining analysis for cytotoxins and phenotyping for CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic T lymphocyte-associated molecules including perforin, granzyme B, granzyme A, and/or expression of CD107a.
811 21377510 In addition, the levels of SIV-specific IgA in saliva and plasma were inversely correlated with viral load at euthanasia.
812 21377510 Interestingly, a marked depletion of CD25(+)FoxP3(+)CD4(+) T cells was observed in the tonsils as well as the intestine of these animals, implying that T regulatory cells may be a major target of SIV infection in infant macaques.