Ignet

Gene Information

Gene symbol: CD86

Gene name: CD86 molecule

HGNC ID: 1705

Synonyms: B7.2, B7-2

Related Genes

#	Gene Symbol	Number of hits
1	ADCYAP1	1 hits
2	ALB	1 hits
3	APC	1 hits
4	B2M	1 hits
5	BCR	1 hits
6	CCR2	1 hits
7	CCR7	1 hits
8	CD14	1 hits
9	CD1A	1 hits
10	CD2	1 hits
11	CD209	1 hits
12	CD274	1 hits
13	CD28	1 hits
14	CD4	1 hits
15	CD40	1 hits
16	CD40LG	1 hits
17	CD44	1 hits
18	CD58	1 hits
19	CD80	1 hits
20	CD83	1 hits
21	CD8A	1 hits
22	CELIAC3	1 hits
23	CR1	1 hits
24	CSF1	1 hits
25	CSF2	1 hits
26	CTLA4	1 hits
27	FCGR2A	1 hits
28	GORASP1	1 hits
29	HLA-A	1 hits
30	HLA-B	1 hits
31	ICAM1	1 hits
32	ICOS	1 hits
33	IDDM2	1 hits
34	IFNA1	1 hits
35	IFNG	1 hits
36	IL10	1 hits
37	IL12A	1 hits
38	IL18	1 hits
39	IL1B	1 hits
40	IL2	1 hits
41	IL2RA	1 hits
42	IL4	1 hits
43	IL6	1 hits
44	IL7	1 hits
45	INS	1 hits
46	ISG20	1 hits
47	ITGA4	1 hits
48	ITGAM	1 hits
49	ITGAX	1 hits
50	ITGB1	1 hits
51	ITGB2	1 hits
52	MRC1	1 hits
53	NFKB1	1 hits
54	PDCD1LG2	1 hits
55	PSIP1	1 hits
56	RELB	1 hits
57	SELL	1 hits
58	SFTPA1	1 hits
59	SH2D1A	1 hits
60	TGFA	1 hits
61	TGFB1	1 hits
62	TMC6	1 hits
63	TNF	1 hits
64	TNFRSF9	1 hits
65	VCAM1	1 hits
66	VEGFA	1 hits
67	VWS	1 hits
68	WARS	1 hits

Related Sentences

#	PMID	Sentence
1	7532678	Insulin-dependent diabetes mellitus (IDDM) is thought to be an immunologically mediated disease resulting in the complete destruction of the insulin-producing islets of Langerhans.
2	7532678	Female NOD mice treated at the onset of insulitis (2-4 wk of age) with CTLA4Ig immunoglobulin (Ig) (a soluble CD28 antagonist) or a monoclonal antibody (mAb) specific for B7-2 (a CD28 ligand) did not develop diabetes.
3	7543497	This pathway can be blocked by CTLA-4-Ig, a soluble form of CTLA-4 which binds with high avidity to the CD28 ligands, B7-1 and B7-2.
4	7543497	Here, we show that CTLA-4-Ig treatment prevents clinical and histological manifestations of disease in a collagen-induced arthritis model of rheumatoid arthritis in the diabetes resistant BB/Wor rat, when therapy is initiated before immunization with bovine type II collagen (BIIC).
5	7543497	Despite the efficacy of CTLA-4-Ig in preventing clinical and histological signs of arthritis and reducing antibody responses to BIIC, delayed type hypersensitivity responses to collagen 18 d or more after CTLA-4-Ig treatment ends are similar in CTLA-4-Ig-treated and untreated rats, suggesting that the prolonged disease suppression observed does not result from induction of T cell anergy.
6	8746558	Likewise, the NOD-derived NIT-1 beta cell line did not express surface B7 or B7-1 mRNA either constitutively or following exposure to IFN-gamma and TNF-alpha, two cytokines known to be present in the insulitis lesion of NOD mice, or cAMP which can induce B7-1 expression on B cells.
7	8746558	By immunohistochemistry and flow cytometry, it was determined that the phenotype of B7+ cells in the pancreas of NOD mice 9 days after cyclophosphamide included a mixture of macrophages and both CD4+ and CD8+ T cells.
8	8746558	RIP-IL-2 transgenic mice, which have extensive islet infiltration but no autoimmune beta cell destruction, also had virtually no B7-1 expression and a minority of B7-2-expressing inflammatory cells.
9	8752897	IFN-alpha induces autoimmune T cells through the induction of intracellular adhesion molecule-1 and B7.2.
10	8752897	We demonstrate that the expression of IFN-alpha by the pancreatic beta cells leads to the development of CD4+ T cells that proliferate in the presence of islet Ags.
11	8752897	We also demonstrate that the pancreatic infiltrating leukocytes in the transgenic mice express increased levels of 87.2 and ICAM-1 and that IFN-alpha can directly induce these two costimulatory molecules on nontransgenic splenic APCs.
12	8752897	Treatment of the transgenic mice with Abs against these costimulatory molecules demonstrated that B7.2 is essential for the induction of autoreactive T cells, whereas ICAM-1 contributes to but is not essential for the formation of these autoreactive cells.
13	8752897	As B7.2 and ICAM-1 are able to synergize to provide costimulatory signals to naive T cells under conditions of limiting Ag, we propose that IFN-alpha expression normally contributes to the development of an anti-viral cellular immune response, but that uncontrolled expression of this cytokine will induce autoimmunity.
14	8752897	IFN-alpha induces autoimmune T cells through the induction of intracellular adhesion molecule-1 and B7.2.
15	8752897	We demonstrate that the expression of IFN-alpha by the pancreatic beta cells leads to the development of CD4+ T cells that proliferate in the presence of islet Ags.
16	8752897	We also demonstrate that the pancreatic infiltrating leukocytes in the transgenic mice express increased levels of 87.2 and ICAM-1 and that IFN-alpha can directly induce these two costimulatory molecules on nontransgenic splenic APCs.
17	8752897	Treatment of the transgenic mice with Abs against these costimulatory molecules demonstrated that B7.2 is essential for the induction of autoreactive T cells, whereas ICAM-1 contributes to but is not essential for the formation of these autoreactive cells.
18	8752897	As B7.2 and ICAM-1 are able to synergize to provide costimulatory signals to naive T cells under conditions of limiting Ag, we propose that IFN-alpha expression normally contributes to the development of an anti-viral cellular immune response, but that uncontrolled expression of this cytokine will induce autoimmunity.
19	8752897	IFN-alpha induces autoimmune T cells through the induction of intracellular adhesion molecule-1 and B7.2.
20	8752897	We demonstrate that the expression of IFN-alpha by the pancreatic beta cells leads to the development of CD4+ T cells that proliferate in the presence of islet Ags.
21	8752897	We also demonstrate that the pancreatic infiltrating leukocytes in the transgenic mice express increased levels of 87.2 and ICAM-1 and that IFN-alpha can directly induce these two costimulatory molecules on nontransgenic splenic APCs.
22	8752897	Treatment of the transgenic mice with Abs against these costimulatory molecules demonstrated that B7.2 is essential for the induction of autoreactive T cells, whereas ICAM-1 contributes to but is not essential for the formation of these autoreactive cells.
23	8752897	As B7.2 and ICAM-1 are able to synergize to provide costimulatory signals to naive T cells under conditions of limiting Ag, we propose that IFN-alpha expression normally contributes to the development of an anti-viral cellular immune response, but that uncontrolled expression of this cytokine will induce autoimmunity.
24	8816976	Islet-infiltrating t lymphocytes in insulin-dependent diabetic patients express CD80 (B7-1) and CD86 (B7-2).
25	8816976	Insulin-dependent diabetes mellitus (IDDM) results mainly from T cell mediated pancreatic beta cell destruction.
26	8816976	One signal is delivered via the antigen specific T cell receptor (TCR) when engaged by major histocompatibility complex presented antigen (MHC:Ag), the other via the T cell's CD28 when engaged by CD80/86.
27	8816976	To further explore whether CD80/86 expression plays a role in IDDM pathogenesis, we analysed pancreatic biopsy specimens from 16 recent-onset IDDM patients (13 men and 3 women; age 29.7 +/- 8.8 years) for CD80/86 expression.
28	8816976	While no biopsy revealed any islet cell specific CD80 or CD86 expression, biopsies from six of the nine patients with insulitis revealed both CD80 and CD86 expression on the islet infiltrating cells.
29	8816976	Of the CD3-positive cells, 19.4% expressed CD80 and 21.7% expressed CD86.
30	8816976	CD80 and CD86-positive cells were similarly distributed throughout the inflamed islets.
31	8816976	These data suggest that CD28 engagement with CD80/86 may play a pathogenic role in the beta cell destruction underlying IDDM.
32	8816976	Islet-infiltrating t lymphocytes in insulin-dependent diabetic patients express CD80 (B7-1) and CD86 (B7-2).
33	8816976	Insulin-dependent diabetes mellitus (IDDM) results mainly from T cell mediated pancreatic beta cell destruction.
34	8816976	One signal is delivered via the antigen specific T cell receptor (TCR) when engaged by major histocompatibility complex presented antigen (MHC:Ag), the other via the T cell's CD28 when engaged by CD80/86.
35	8816976	To further explore whether CD80/86 expression plays a role in IDDM pathogenesis, we analysed pancreatic biopsy specimens from 16 recent-onset IDDM patients (13 men and 3 women; age 29.7 +/- 8.8 years) for CD80/86 expression.
36	8816976	While no biopsy revealed any islet cell specific CD80 or CD86 expression, biopsies from six of the nine patients with insulitis revealed both CD80 and CD86 expression on the islet infiltrating cells.
37	8816976	Of the CD3-positive cells, 19.4% expressed CD80 and 21.7% expressed CD86.
38	8816976	CD80 and CD86-positive cells were similarly distributed throughout the inflamed islets.
39	8816976	These data suggest that CD28 engagement with CD80/86 may play a pathogenic role in the beta cell destruction underlying IDDM.
40	8816976	Islet-infiltrating t lymphocytes in insulin-dependent diabetic patients express CD80 (B7-1) and CD86 (B7-2).
41	8816976	Insulin-dependent diabetes mellitus (IDDM) results mainly from T cell mediated pancreatic beta cell destruction.
42	8816976	One signal is delivered via the antigen specific T cell receptor (TCR) when engaged by major histocompatibility complex presented antigen (MHC:Ag), the other via the T cell's CD28 when engaged by CD80/86.
43	8816976	To further explore whether CD80/86 expression plays a role in IDDM pathogenesis, we analysed pancreatic biopsy specimens from 16 recent-onset IDDM patients (13 men and 3 women; age 29.7 +/- 8.8 years) for CD80/86 expression.
44	8816976	While no biopsy revealed any islet cell specific CD80 or CD86 expression, biopsies from six of the nine patients with insulitis revealed both CD80 and CD86 expression on the islet infiltrating cells.
45	8816976	Of the CD3-positive cells, 19.4% expressed CD80 and 21.7% expressed CD86.
46	8816976	CD80 and CD86-positive cells were similarly distributed throughout the inflamed islets.
47	8816976	These data suggest that CD28 engagement with CD80/86 may play a pathogenic role in the beta cell destruction underlying IDDM.
48	8816976	Islet-infiltrating t lymphocytes in insulin-dependent diabetic patients express CD80 (B7-1) and CD86 (B7-2).
49	8816976	Insulin-dependent diabetes mellitus (IDDM) results mainly from T cell mediated pancreatic beta cell destruction.
50	8816976	One signal is delivered via the antigen specific T cell receptor (TCR) when engaged by major histocompatibility complex presented antigen (MHC:Ag), the other via the T cell's CD28 when engaged by CD80/86.
51	8816976	To further explore whether CD80/86 expression plays a role in IDDM pathogenesis, we analysed pancreatic biopsy specimens from 16 recent-onset IDDM patients (13 men and 3 women; age 29.7 +/- 8.8 years) for CD80/86 expression.
52	8816976	While no biopsy revealed any islet cell specific CD80 or CD86 expression, biopsies from six of the nine patients with insulitis revealed both CD80 and CD86 expression on the islet infiltrating cells.
53	8816976	Of the CD3-positive cells, 19.4% expressed CD80 and 21.7% expressed CD86.
54	8816976	CD80 and CD86-positive cells were similarly distributed throughout the inflamed islets.
55	8816976	These data suggest that CD28 engagement with CD80/86 may play a pathogenic role in the beta cell destruction underlying IDDM.
56	8899799	Appearance of cells expressing CD80 and CD86 costimulatory antigens in the pancreas of nonobese diabetic mice.
57	8899799	The immunoregulatory effects of the costimulatory CD80/B7-1 and CD86/B7-2 antigens expressed by the antigen-presenting cells may be crucial for the development of immune responses and their absence may lead to clonal anergy, which is important in the prevention of autoimmune reactivity.
58	8899799	To evaluate the role of the CD80 and CD86 antigens in the development of insulin-dependent diabetes mellitus, expression of these antigens in the pancreas of normal and nonobese diabetic mice was studied.
59	8899799	The pancreata of normal BALB/c mice and young nonobese diabetic mice contained no CD80- or CD86-positive cells.
60	8899799	CD80- and CD86-positive cells appeared in the pancreas of nonobese diabetic mice by 6 weeks of age.
61	8899799	Double immunostaining at the age of 12 weeks showed that CD80-positive cells accumulated around the islets of Langerhans but no insulin-containing cells expressed the costimulatory molecules.
62	8899799	The morphology of the CD80- and CD86-positive cells was heterogeneous.
63	8899799	Many were Mac-1 integrin (CD11b/CD18) positive, suggesting that macrophages expressing the costimulatory antigens are present in the pancreas of all nonobese diabetic mice by 12 weeks of age and that CD80- and CD86-expressing macrophages may be involved in the local regulation of antiislet immune responses.
64	8899799	Appearance of cells expressing CD80 and CD86 costimulatory antigens in the pancreas of nonobese diabetic mice.
65	8899799	The immunoregulatory effects of the costimulatory CD80/B7-1 and CD86/B7-2 antigens expressed by the antigen-presenting cells may be crucial for the development of immune responses and their absence may lead to clonal anergy, which is important in the prevention of autoimmune reactivity.
66	8899799	To evaluate the role of the CD80 and CD86 antigens in the development of insulin-dependent diabetes mellitus, expression of these antigens in the pancreas of normal and nonobese diabetic mice was studied.
67	8899799	The pancreata of normal BALB/c mice and young nonobese diabetic mice contained no CD80- or CD86-positive cells.
68	8899799	CD80- and CD86-positive cells appeared in the pancreas of nonobese diabetic mice by 6 weeks of age.
69	8899799	Double immunostaining at the age of 12 weeks showed that CD80-positive cells accumulated around the islets of Langerhans but no insulin-containing cells expressed the costimulatory molecules.
70	8899799	The morphology of the CD80- and CD86-positive cells was heterogeneous.
71	8899799	Many were Mac-1 integrin (CD11b/CD18) positive, suggesting that macrophages expressing the costimulatory antigens are present in the pancreas of all nonobese diabetic mice by 12 weeks of age and that CD80- and CD86-expressing macrophages may be involved in the local regulation of antiislet immune responses.
72	8899799	Appearance of cells expressing CD80 and CD86 costimulatory antigens in the pancreas of nonobese diabetic mice.
73	8899799	The immunoregulatory effects of the costimulatory CD80/B7-1 and CD86/B7-2 antigens expressed by the antigen-presenting cells may be crucial for the development of immune responses and their absence may lead to clonal anergy, which is important in the prevention of autoimmune reactivity.
74	8899799	To evaluate the role of the CD80 and CD86 antigens in the development of insulin-dependent diabetes mellitus, expression of these antigens in the pancreas of normal and nonobese diabetic mice was studied.
75	8899799	The pancreata of normal BALB/c mice and young nonobese diabetic mice contained no CD80- or CD86-positive cells.
76	8899799	CD80- and CD86-positive cells appeared in the pancreas of nonobese diabetic mice by 6 weeks of age.
77	8899799	Double immunostaining at the age of 12 weeks showed that CD80-positive cells accumulated around the islets of Langerhans but no insulin-containing cells expressed the costimulatory molecules.
78	8899799	The morphology of the CD80- and CD86-positive cells was heterogeneous.
79	8899799	Many were Mac-1 integrin (CD11b/CD18) positive, suggesting that macrophages expressing the costimulatory antigens are present in the pancreas of all nonobese diabetic mice by 12 weeks of age and that CD80- and CD86-expressing macrophages may be involved in the local regulation of antiislet immune responses.
80	8899799	Appearance of cells expressing CD80 and CD86 costimulatory antigens in the pancreas of nonobese diabetic mice.
81	8899799	The immunoregulatory effects of the costimulatory CD80/B7-1 and CD86/B7-2 antigens expressed by the antigen-presenting cells may be crucial for the development of immune responses and their absence may lead to clonal anergy, which is important in the prevention of autoimmune reactivity.
82	8899799	To evaluate the role of the CD80 and CD86 antigens in the development of insulin-dependent diabetes mellitus, expression of these antigens in the pancreas of normal and nonobese diabetic mice was studied.
83	8899799	The pancreata of normal BALB/c mice and young nonobese diabetic mice contained no CD80- or CD86-positive cells.
84	8899799	CD80- and CD86-positive cells appeared in the pancreas of nonobese diabetic mice by 6 weeks of age.
85	8899799	Double immunostaining at the age of 12 weeks showed that CD80-positive cells accumulated around the islets of Langerhans but no insulin-containing cells expressed the costimulatory molecules.
86	8899799	The morphology of the CD80- and CD86-positive cells was heterogeneous.
87	8899799	Many were Mac-1 integrin (CD11b/CD18) positive, suggesting that macrophages expressing the costimulatory antigens are present in the pancreas of all nonobese diabetic mice by 12 weeks of age and that CD80- and CD86-expressing macrophages may be involved in the local regulation of antiislet immune responses.
88	8899799	Appearance of cells expressing CD80 and CD86 costimulatory antigens in the pancreas of nonobese diabetic mice.
89	8899799	The immunoregulatory effects of the costimulatory CD80/B7-1 and CD86/B7-2 antigens expressed by the antigen-presenting cells may be crucial for the development of immune responses and their absence may lead to clonal anergy, which is important in the prevention of autoimmune reactivity.
90	8899799	To evaluate the role of the CD80 and CD86 antigens in the development of insulin-dependent diabetes mellitus, expression of these antigens in the pancreas of normal and nonobese diabetic mice was studied.
91	8899799	The pancreata of normal BALB/c mice and young nonobese diabetic mice contained no CD80- or CD86-positive cells.
92	8899799	CD80- and CD86-positive cells appeared in the pancreas of nonobese diabetic mice by 6 weeks of age.
93	8899799	Double immunostaining at the age of 12 weeks showed that CD80-positive cells accumulated around the islets of Langerhans but no insulin-containing cells expressed the costimulatory molecules.
94	8899799	The morphology of the CD80- and CD86-positive cells was heterogeneous.
95	8899799	Many were Mac-1 integrin (CD11b/CD18) positive, suggesting that macrophages expressing the costimulatory antigens are present in the pancreas of all nonobese diabetic mice by 12 weeks of age and that CD80- and CD86-expressing macrophages may be involved in the local regulation of antiislet immune responses.
96	8899799	Appearance of cells expressing CD80 and CD86 costimulatory antigens in the pancreas of nonobese diabetic mice.
97	8899799	The immunoregulatory effects of the costimulatory CD80/B7-1 and CD86/B7-2 antigens expressed by the antigen-presenting cells may be crucial for the development of immune responses and their absence may lead to clonal anergy, which is important in the prevention of autoimmune reactivity.
98	8899799	To evaluate the role of the CD80 and CD86 antigens in the development of insulin-dependent diabetes mellitus, expression of these antigens in the pancreas of normal and nonobese diabetic mice was studied.
99	8899799	The pancreata of normal BALB/c mice and young nonobese diabetic mice contained no CD80- or CD86-positive cells.
100	8899799	CD80- and CD86-positive cells appeared in the pancreas of nonobese diabetic mice by 6 weeks of age.
101	8899799	Double immunostaining at the age of 12 weeks showed that CD80-positive cells accumulated around the islets of Langerhans but no insulin-containing cells expressed the costimulatory molecules.
102	8899799	The morphology of the CD80- and CD86-positive cells was heterogeneous.
103	8899799	Many were Mac-1 integrin (CD11b/CD18) positive, suggesting that macrophages expressing the costimulatory antigens are present in the pancreas of all nonobese diabetic mice by 12 weeks of age and that CD80- and CD86-expressing macrophages may be involved in the local regulation of antiislet immune responses.
104	8899799	Appearance of cells expressing CD80 and CD86 costimulatory antigens in the pancreas of nonobese diabetic mice.
105	8899799	The immunoregulatory effects of the costimulatory CD80/B7-1 and CD86/B7-2 antigens expressed by the antigen-presenting cells may be crucial for the development of immune responses and their absence may lead to clonal anergy, which is important in the prevention of autoimmune reactivity.
106	8899799	To evaluate the role of the CD80 and CD86 antigens in the development of insulin-dependent diabetes mellitus, expression of these antigens in the pancreas of normal and nonobese diabetic mice was studied.
107	8899799	The pancreata of normal BALB/c mice and young nonobese diabetic mice contained no CD80- or CD86-positive cells.
108	8899799	CD80- and CD86-positive cells appeared in the pancreas of nonobese diabetic mice by 6 weeks of age.
109	8899799	Double immunostaining at the age of 12 weeks showed that CD80-positive cells accumulated around the islets of Langerhans but no insulin-containing cells expressed the costimulatory molecules.
110	8899799	The morphology of the CD80- and CD86-positive cells was heterogeneous.
111	8899799	Many were Mac-1 integrin (CD11b/CD18) positive, suggesting that macrophages expressing the costimulatory antigens are present in the pancreas of all nonobese diabetic mice by 12 weeks of age and that CD80- and CD86-expressing macrophages may be involved in the local regulation of antiislet immune responses.
112	8993020	We, therefore, have examined the role of CD28/B7 interactions in a model of insulin-dependent diabetes mellitus in which T cell-dependent insulitis and hyperglycemia occur over a brief period, following multiple low doses of streptozotocin (multidose streptozotocin (STZ)-induced diabetes mellitus).
113	8993020	Expression of CD28 was necessary for diabetes because CD28 -/- C57BL/KsJ animals developed neither hyperglycemia nor insulitis, and did not express IFN-gamma mRNA following STZ, unlike CD28 +/- C57BL/KsJ mice.
114	8993020	The expression of B7-1 (CD80) and B7-2 (CD86) molecules was closely regulated during development of the disease.
115	8993020	Expression of both CD80 and CD86 increased on cells in pancreatic lymph nodes in STZ-treated C57BL/KsJ mice.
116	8993020	In wild-type animals, treatment with mAb against CD86 prevented, whereas treatment with mAb against CD80 exacerbated, insulitis and hyperglycemia, indicating that mAbs against these molecules differentially affect development of disease.
117	8993020	CD80 and CD86 molecules, the CD28/CTLA4 ligands, may have different roles in regulation of the disease and affect T cell function at steps beyond differentiation into mature phenotypes.
118	8993020	We, therefore, have examined the role of CD28/B7 interactions in a model of insulin-dependent diabetes mellitus in which T cell-dependent insulitis and hyperglycemia occur over a brief period, following multiple low doses of streptozotocin (multidose streptozotocin (STZ)-induced diabetes mellitus).
119	8993020	Expression of CD28 was necessary for diabetes because CD28 -/- C57BL/KsJ animals developed neither hyperglycemia nor insulitis, and did not express IFN-gamma mRNA following STZ, unlike CD28 +/- C57BL/KsJ mice.
120	8993020	The expression of B7-1 (CD80) and B7-2 (CD86) molecules was closely regulated during development of the disease.
121	8993020	Expression of both CD80 and CD86 increased on cells in pancreatic lymph nodes in STZ-treated C57BL/KsJ mice.
122	8993020	In wild-type animals, treatment with mAb against CD86 prevented, whereas treatment with mAb against CD80 exacerbated, insulitis and hyperglycemia, indicating that mAbs against these molecules differentially affect development of disease.
123	8993020	CD80 and CD86 molecules, the CD28/CTLA4 ligands, may have different roles in regulation of the disease and affect T cell function at steps beyond differentiation into mature phenotypes.
124	8993020	We, therefore, have examined the role of CD28/B7 interactions in a model of insulin-dependent diabetes mellitus in which T cell-dependent insulitis and hyperglycemia occur over a brief period, following multiple low doses of streptozotocin (multidose streptozotocin (STZ)-induced diabetes mellitus).
125	8993020	Expression of CD28 was necessary for diabetes because CD28 -/- C57BL/KsJ animals developed neither hyperglycemia nor insulitis, and did not express IFN-gamma mRNA following STZ, unlike CD28 +/- C57BL/KsJ mice.
126	8993020	The expression of B7-1 (CD80) and B7-2 (CD86) molecules was closely regulated during development of the disease.
127	8993020	Expression of both CD80 and CD86 increased on cells in pancreatic lymph nodes in STZ-treated C57BL/KsJ mice.
128	8993020	In wild-type animals, treatment with mAb against CD86 prevented, whereas treatment with mAb against CD80 exacerbated, insulitis and hyperglycemia, indicating that mAbs against these molecules differentially affect development of disease.
129	8993020	CD80 and CD86 molecules, the CD28/CTLA4 ligands, may have different roles in regulation of the disease and affect T cell function at steps beyond differentiation into mature phenotypes.
130	8993020	We, therefore, have examined the role of CD28/B7 interactions in a model of insulin-dependent diabetes mellitus in which T cell-dependent insulitis and hyperglycemia occur over a brief period, following multiple low doses of streptozotocin (multidose streptozotocin (STZ)-induced diabetes mellitus).
131	8993020	Expression of CD28 was necessary for diabetes because CD28 -/- C57BL/KsJ animals developed neither hyperglycemia nor insulitis, and did not express IFN-gamma mRNA following STZ, unlike CD28 +/- C57BL/KsJ mice.
132	8993020	The expression of B7-1 (CD80) and B7-2 (CD86) molecules was closely regulated during development of the disease.
133	8993020	Expression of both CD80 and CD86 increased on cells in pancreatic lymph nodes in STZ-treated C57BL/KsJ mice.
134	8993020	In wild-type animals, treatment with mAb against CD86 prevented, whereas treatment with mAb against CD80 exacerbated, insulitis and hyperglycemia, indicating that mAbs against these molecules differentially affect development of disease.
135	8993020	CD80 and CD86 molecules, the CD28/CTLA4 ligands, may have different roles in regulation of the disease and affect T cell function at steps beyond differentiation into mature phenotypes.
136	9724775	Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM).
137	9724775	Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci.
138	9724775	Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition.
139	9725204	Autoimmunity without diabetes in transgenic mice expressing beta cell-specific CD86, but not CD80: parameters that trigger progression to diabetes.
140	9725204	To define more clearly the roles of CD80 (RIP-CD80) and CD86 (RIP-CD86) in the activation of autoreactive T cells in vivo, we generated transgenic mice expressing either or both costimulatory molecules on the beta cells of the pancreas.
141	9725204	While RIP-CD80 mice do not show any sign of autoimmunity, at the age of 7 mo RIP-CD86 transgenic mice develop a lymphoid infiltrate with both IFN-gamma- and IL-4-positive cells in the vicinity of the islets; these mice, however, never progress to diabetes.
142	9725204	This fundamental difference in the ability of CD80 and CD86 to activate self-reactive T cells in vivo is, however, obliterated when the level of TCR signaling is increased by either TNF-alpha or transgenic MHC class II expression.
143	9725204	These results support the suggestion that CD80 and CD86 mainly differ at the level of the intensity of the signals they deliver.
144	9725204	Autoimmunity without diabetes in transgenic mice expressing beta cell-specific CD86, but not CD80: parameters that trigger progression to diabetes.
145	9725204	To define more clearly the roles of CD80 (RIP-CD80) and CD86 (RIP-CD86) in the activation of autoreactive T cells in vivo, we generated transgenic mice expressing either or both costimulatory molecules on the beta cells of the pancreas.
146	9725204	While RIP-CD80 mice do not show any sign of autoimmunity, at the age of 7 mo RIP-CD86 transgenic mice develop a lymphoid infiltrate with both IFN-gamma- and IL-4-positive cells in the vicinity of the islets; these mice, however, never progress to diabetes.
147	9725204	This fundamental difference in the ability of CD80 and CD86 to activate self-reactive T cells in vivo is, however, obliterated when the level of TCR signaling is increased by either TNF-alpha or transgenic MHC class II expression.
148	9725204	These results support the suggestion that CD80 and CD86 mainly differ at the level of the intensity of the signals they deliver.
149	9725204	Autoimmunity without diabetes in transgenic mice expressing beta cell-specific CD86, but not CD80: parameters that trigger progression to diabetes.
150	9725204	To define more clearly the roles of CD80 (RIP-CD80) and CD86 (RIP-CD86) in the activation of autoreactive T cells in vivo, we generated transgenic mice expressing either or both costimulatory molecules on the beta cells of the pancreas.
151	9725204	While RIP-CD80 mice do not show any sign of autoimmunity, at the age of 7 mo RIP-CD86 transgenic mice develop a lymphoid infiltrate with both IFN-gamma- and IL-4-positive cells in the vicinity of the islets; these mice, however, never progress to diabetes.
152	9725204	This fundamental difference in the ability of CD80 and CD86 to activate self-reactive T cells in vivo is, however, obliterated when the level of TCR signaling is increased by either TNF-alpha or transgenic MHC class II expression.
153	9725204	These results support the suggestion that CD80 and CD86 mainly differ at the level of the intensity of the signals they deliver.
154	9725204	Autoimmunity without diabetes in transgenic mice expressing beta cell-specific CD86, but not CD80: parameters that trigger progression to diabetes.
155	9725204	To define more clearly the roles of CD80 (RIP-CD80) and CD86 (RIP-CD86) in the activation of autoreactive T cells in vivo, we generated transgenic mice expressing either or both costimulatory molecules on the beta cells of the pancreas.
156	9725204	While RIP-CD80 mice do not show any sign of autoimmunity, at the age of 7 mo RIP-CD86 transgenic mice develop a lymphoid infiltrate with both IFN-gamma- and IL-4-positive cells in the vicinity of the islets; these mice, however, never progress to diabetes.
157	9725204	This fundamental difference in the ability of CD80 and CD86 to activate self-reactive T cells in vivo is, however, obliterated when the level of TCR signaling is increased by either TNF-alpha or transgenic MHC class II expression.
158	9725204	These results support the suggestion that CD80 and CD86 mainly differ at the level of the intensity of the signals they deliver.
159	9725265	Humans with pancreatic islet autoimmunity at high risk for insulin-dependent diabetes mellitus (IDDM) present the opportunity to investigate DC in autoimmune disease.
160	9725265	While the DC phenotype, HLA-DR+CD14-, was expressed by > or =90% of the cells generated from relatives and controls, the proportion of cells that expressed CD1a and the costimulator molecules CD80 (B7-1) and CD86 (B7-2) was significantly lower in IDDM relatives.
161	9725265	In addition, B7-1 and B7-2 expression per cell was significantly lower in IDDM relatives.
162	9725265	Humans with pancreatic islet autoimmunity at high risk for insulin-dependent diabetes mellitus (IDDM) present the opportunity to investigate DC in autoimmune disease.
163	9725265	While the DC phenotype, HLA-DR+CD14-, was expressed by > or =90% of the cells generated from relatives and controls, the proportion of cells that expressed CD1a and the costimulator molecules CD80 (B7-1) and CD86 (B7-2) was significantly lower in IDDM relatives.
164	9725265	In addition, B7-1 and B7-2 expression per cell was significantly lower in IDDM relatives.
165	9741460	In an attempt to prevent rejection, we used cyclophosphamide (CP), a powerful anti-B cell agent, or CTLA4Ig, an inhibitor of T-cell co-stimulation [via B7-1 (CD80) and B7-2 (CD86)], either given in combination with anti-CD4 (GK1.5) or anti-CD3 (KT3) MAb to the recipient mice.
166	10206487	The role of CD8+ cells, cell degeneration, and Fas ligand in insulitis after intraperitoneal transfer of NOD splenocytes.
167	10206487	Cells expressing CD4, CD8, CD18, CD49d/CD29, CD44, CD54, CD80, CD86, CD106, CD11b/CD18 or DNA breaks were stained in the pancreases of female or male scid/ scid mice after adoptive transfer of lymphocytes from older than 12-week female nonobese diabetic (NOD) or Balb/c mice.
168	10206487	After intraperitoneal adoptive transfer of NOD splenocytes to female severe combined immunodeficiency (scid)/scid mice, in situ end labeling (ISEL)+ as well as CD80+ and CD86+ cell infiltrates appeared first in the blood vessel walls and pancreatic interstitial tissue at 2-3 weeks after transfer.
169	10206487	CD4+, CD8+, CD18+, CD44+, CD54+, and CD106+ cells then encircled and invaded some islets of the scid/scid mice 2 to 7 weeks after transfer.
170	10206487	Fas ligand was not present in Western blotting.
171	10206487	It is proposed that apoptosis commonly occurs in islet-infiltrating lymphocytes and that in the scid/scid adoptive-transfer model, the first islet-infiltrating cells are destroyed by programmed cell death independent of Fas ligand.
172	10206487	The role of CD8+ cells, cell degeneration, and Fas ligand in insulitis after intraperitoneal transfer of NOD splenocytes.
173	10206487	Cells expressing CD4, CD8, CD18, CD49d/CD29, CD44, CD54, CD80, CD86, CD106, CD11b/CD18 or DNA breaks were stained in the pancreases of female or male scid/ scid mice after adoptive transfer of lymphocytes from older than 12-week female nonobese diabetic (NOD) or Balb/c mice.
174	10206487	After intraperitoneal adoptive transfer of NOD splenocytes to female severe combined immunodeficiency (scid)/scid mice, in situ end labeling (ISEL)+ as well as CD80+ and CD86+ cell infiltrates appeared first in the blood vessel walls and pancreatic interstitial tissue at 2-3 weeks after transfer.
175	10206487	CD4+, CD8+, CD18+, CD44+, CD54+, and CD106+ cells then encircled and invaded some islets of the scid/scid mice 2 to 7 weeks after transfer.
176	10206487	Fas ligand was not present in Western blotting.
177	10206487	It is proposed that apoptosis commonly occurs in islet-infiltrating lymphocytes and that in the scid/scid adoptive-transfer model, the first islet-infiltrating cells are destroyed by programmed cell death independent of Fas ligand.
178	10580417	DCs derived from GM-CSF [granulocyte/macrophage colony-stimulating factor] + interleukin (IL)-4 cultures expressed high levels of major histocompatibility complex (MHC) class II, CD40, CD80, and CD86 molecules and were efficient stimulators of naive allogeneic T-cells.
179	10580417	In contrast, DCs derived from GM-CSF cultures had low levels of MHC class II costimulation/activation molecules, were able to take up mannosylated bovine serum albumin more efficiently than GM + IL-4 DCs, and were poor T-cell stimulators.
180	10679081	Low CD86 expression in the nonobese diabetic mouse results in the impairment of both T cell activation and CTLA-4 up-regulation.
181	10679081	It was found that NOD macrophages, dendritic cells, and T cells, but not B cells, expressed lower basal levels of CD86, but not CD80, CD28, or CD40, compared with C57BL/6 and BALB/c.
182	10679081	Furthermore, following activation, the relative up-regulation of CTLA-4, as compared with CD28, was more pronounced on C57BL/6 and BALB/c T cells as shown by an increased CTLA-4/CD28 ratio.
183	10679081	This activation-induced increase in the CTLA-4/CD28 ratio was markedly reduced on NOD T cells compared with the other two strains.
184	10679081	The low CD86 expression in NOD mice may account for the reduced increase in both proliferation and the CTLA-4/CD28 ratio, since reducing CD86 expression in C57BL/6 and BALB/c cultures to NOD levels significantly reduces the proliferation and the CTLA-4/CD28 ratio.
185	10679081	Therefore, we propose that a low level of CD86 expression in the NOD mouse contributes to a defective regulation of autoreactive T cells by preventing the full activation of T cells and therefore the up-regulation of CTLA-4.
186	10679081	Low CD86 expression in the nonobese diabetic mouse results in the impairment of both T cell activation and CTLA-4 up-regulation.
187	10679081	It was found that NOD macrophages, dendritic cells, and T cells, but not B cells, expressed lower basal levels of CD86, but not CD80, CD28, or CD40, compared with C57BL/6 and BALB/c.
188	10679081	Furthermore, following activation, the relative up-regulation of CTLA-4, as compared with CD28, was more pronounced on C57BL/6 and BALB/c T cells as shown by an increased CTLA-4/CD28 ratio.
189	10679081	This activation-induced increase in the CTLA-4/CD28 ratio was markedly reduced on NOD T cells compared with the other two strains.
190	10679081	The low CD86 expression in NOD mice may account for the reduced increase in both proliferation and the CTLA-4/CD28 ratio, since reducing CD86 expression in C57BL/6 and BALB/c cultures to NOD levels significantly reduces the proliferation and the CTLA-4/CD28 ratio.
191	10679081	Therefore, we propose that a low level of CD86 expression in the NOD mouse contributes to a defective regulation of autoreactive T cells by preventing the full activation of T cells and therefore the up-regulation of CTLA-4.
192	10679081	Low CD86 expression in the nonobese diabetic mouse results in the impairment of both T cell activation and CTLA-4 up-regulation.
193	10679081	It was found that NOD macrophages, dendritic cells, and T cells, but not B cells, expressed lower basal levels of CD86, but not CD80, CD28, or CD40, compared with C57BL/6 and BALB/c.
194	10679081	Furthermore, following activation, the relative up-regulation of CTLA-4, as compared with CD28, was more pronounced on C57BL/6 and BALB/c T cells as shown by an increased CTLA-4/CD28 ratio.
195	10679081	This activation-induced increase in the CTLA-4/CD28 ratio was markedly reduced on NOD T cells compared with the other two strains.
196	10679081	The low CD86 expression in NOD mice may account for the reduced increase in both proliferation and the CTLA-4/CD28 ratio, since reducing CD86 expression in C57BL/6 and BALB/c cultures to NOD levels significantly reduces the proliferation and the CTLA-4/CD28 ratio.
197	10679081	Therefore, we propose that a low level of CD86 expression in the NOD mouse contributes to a defective regulation of autoreactive T cells by preventing the full activation of T cells and therefore the up-regulation of CTLA-4.
198	10679081	Low CD86 expression in the nonobese diabetic mouse results in the impairment of both T cell activation and CTLA-4 up-regulation.
199	10679081	It was found that NOD macrophages, dendritic cells, and T cells, but not B cells, expressed lower basal levels of CD86, but not CD80, CD28, or CD40, compared with C57BL/6 and BALB/c.
200	10679081	Furthermore, following activation, the relative up-regulation of CTLA-4, as compared with CD28, was more pronounced on C57BL/6 and BALB/c T cells as shown by an increased CTLA-4/CD28 ratio.
201	10679081	This activation-induced increase in the CTLA-4/CD28 ratio was markedly reduced on NOD T cells compared with the other two strains.
202	10679081	The low CD86 expression in NOD mice may account for the reduced increase in both proliferation and the CTLA-4/CD28 ratio, since reducing CD86 expression in C57BL/6 and BALB/c cultures to NOD levels significantly reduces the proliferation and the CTLA-4/CD28 ratio.
203	10679081	Therefore, we propose that a low level of CD86 expression in the NOD mouse contributes to a defective regulation of autoreactive T cells by preventing the full activation of T cells and therefore the up-regulation of CTLA-4.
204	10766456	Double-staining studies using confocal laser scanning microscopy showed that the CD11c-positive DCs coexpress both major histocompatibility (MHC) class II and costimulatory molecules, CD80 and CD86.
205	10795741	B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes.
206	10795741	In sharp contrast, spontaneous diabetes is exacerbated in both B7-1/B7-2-deficient and CD28-deficient NOD mice.
207	10795741	These mice present a profound decrease of the immunoregulatory CD4+CD25+ T cells, which control diabetes in prediabetic NOD mice.
208	10803701	NOD dendritic cells showed lower expressions of MHC class II, B7-1, B7-2 and CD40, compared with C57BL/6 dendritic cells.
209	11069063	We show that exposure of MODC to IS-PL, but not IS-ODN, induced a dose-dependent strong up-regulation of HLA class II and co-stimulatory molecules (CD80, CD86), similar to that observed after treatment with TNF-alpha.
210	11069063	Functional activity was assessed by the detection of increased secretions of IL-6 and IL-12(p75) following treatment with IS-PL.
211	11069063	T cells stimulated by tetanus toxoid-pulsed, IS-PL-matured MODC were significantly more frequently IFN-gamma positive (25.2+/-2.7%) as compared to TNF-alpha-treated MODC (15.4+/-1.4%), indicating a strong activation of Th1 lymphocytes.
212	11175852	Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses.
213	11175852	IL-4-influenced DC produce distinct effects on CD8+ T cells depending on their state of activation.
214	11175852	Our findings demonstrate that B7.2 induces expansion of CD8+ T cells and B7.1 governs their acquisition of cytolytic activity.
215	11222507	CD28 co-stimulation restores T cell responsiveness in NOD mice by overcoming deficiencies in Rac-1/p38 mitogen-activated protein kinase signaling and IL-2 and IL-4 gene transcription.
216	11222507	Neonatal CD28 co-stimulation reverses T cell hyporesponsiveness and protects NOD mice from diabetes by an IL-4-mediated mechanism, indicating that a deficiency in TCR signaling may be overcome by CD28/B7-2 co-stimulation in NOD T cells.
217	11222507	To investigate which co-stimulation-induced signaling events mediate this protection, we analyzed the activity of Ras, Rac-1, mitogen-activated protein kinases (MAPK) and several transcription factors in TCR-activated NOD T cells in the presence or absence of CD28 co-stimulation.
218	11222507	We show that CD28 co-stimulation restores normal TCR-induced activation of Rac-1 and p38 MAPK in NOD T cells.
219	11222507	Deficiencies in TCR-induced nuclear expression of activating protein (AP)-1 binding proteins as well as activation of AP-1 and NF-AT in the IL-2 and IL-4 P1 promoters are also corrected by CD28 co-stimulation.
220	11222507	Thus, CD28 co-stimulation reverses NOD T cell hyporesponsiveness by restoring TCR signaling leading to the activation of AP-1 and NF-AT during IL-2 and IL-4 gene transcription.
221	11244036	Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation.
222	11244036	In this review, we summarize the current understanding of these complex costimulatory pathways including the individual roles of the CD28, CTLA-4, B7-1 (CD80), and B7-2 (CD86) molecules.
223	11244036	This is most apparent in regulation of the CD4(+)CD25(+)CTLA-4(+) immunoregulatory T cells that control multiple autoimmune diseases.
224	11261783	After such enhanced clustering the DCs had increased their T cell stimulating capabilities in syngeneic mixed lymphocyte reaction, and had a higher expression of CD80 and CD86 (signs of maturation).
225	11298122	NOD DC, in contrast to CBA DC, have very low levels of intracellular I-A molecules and cell surface expression of MHC class II, CD80, CD86 and CD40 but normal beta 2-microglobulin expression.
226	11298122	Incubation with the strong inflammatory stimulus of LPS and IFN-gamma does not increase class II MHC, CD80 or CD86, but upregulates the level of CD40.
227	11298122	However all the DC irrespective of origin were able to produce TNF-alpha, IL-6, low levels of IL-12(p70) and NO in response to LPS plus IFN-gamma.
228	11298122	A gene or genes specific to the NOD strain, but outside the MHC region, therefore must regulate the differentiation of DC in response to GM-CSF.
229	11298122	NOD DC, in contrast to CBA DC, have very low levels of intracellular I-A molecules and cell surface expression of MHC class II, CD80, CD86 and CD40 but normal beta 2-microglobulin expression.
230	11298122	Incubation with the strong inflammatory stimulus of LPS and IFN-gamma does not increase class II MHC, CD80 or CD86, but upregulates the level of CD40.
231	11298122	However all the DC irrespective of origin were able to produce TNF-alpha, IL-6, low levels of IL-12(p70) and NO in response to LPS plus IFN-gamma.
232	11298122	A gene or genes specific to the NOD strain, but outside the MHC region, therefore must regulate the differentiation of DC in response to GM-CSF.
233	11535635	The peripheral nerve tissue was infiltrated with dendritic cells, CD4(+), and CD8(+) T cells.
234	11535635	This model demonstrates that NOD mice have "cryptic" autoimmune defects that can polarize toward the nervous tissue after the selective disruption of CD28/B7-2 costimulatory pathway.
235	11860706	Cytotoxic T lymphocyte antigen 4 (CTLA-4 or CD152) is a strong negative regulator of T cell activity.
236	11860706	Like CD28 (a positive regulator) it binds to B7-1 and B7-2, and there is no known natural selective ligand.
237	11860706	However, a single amino acid substitution in B7-1 (W88 > A; denoted B7-1wa) abrogates binding to CD28 but not to CTLA-4.
238	11860706	Interferon-gamma and interleukin-4 were both depressed, arguing against a Th2 bias.
239	11927616	We found that in patients with new-onset type 1 diabetes, GAD65-reactive T cells were strikingly less dependent on CD28 and B7-1 costimulation to enter into cell cycle and proliferate than were equivalent cells derived from healthy controls.
240	11927616	In addition, we observed different effects with selective blockade of either B7-1 or B7-2 molecules; B7-1 appears to deliver a negative signal by engaging CTLA-4, while B7-2 engagement of CD28 upregulates T cell proliferation and cytokine secretion.
241	12173299	In parallel, the proliferative response of CD4+ T-cells to the primary protein antigens keyhole limpet hemocyanin (KLH) and sperm whale myoglobin (SWM) was measured in vitro using monocyte-derived dendritic cells (MDDC) as antigen-presenting cells.
242	12173299	Antigen-induced interferon-gamma and interleukin-13 release was reduced in type-1 diabetes patients, localizing the impairment to the level of antigen-presenting cell-T-cell interaction.
243	12173299	FACS analysis of CD80 (B7.1), CD86 (B7.2), and HLA-DR expression on MDDC could not demonstrate significant differences in the expression of these molecules between type-1 and type-2 diabetes patients and healthy controls.
244	12419283	The expressions of the co-stimulatory molecules B7-2 and ICAM-1 were significantly increased in spleen cells of rIFN-gamma treated mice while the expression of MHC class I was decreased.
245	12419283	In vitro studies demonstrated that NOD mouse mononuclear spleen cells preincubated with rIFN-gamma and subsequently cocultured with responder cells, potently inhibited responder T-cell proliferative responses. rIFN-gamma administration decreased IL-12 and IL-2 mRNA expression in spleen cells while increasing IL-1 expression.
246	12483990	DC maturation was monitored by flow cytometric analyses for the expression of surface markers (HLA-DR, CD1a, CD40, CD80, CD86, CD83, CD14, CD32, mannose-receptor, and CD11c).
247	12483990	Solely, a marginal, but significant, transient down-regulation of CD1a on Day 3 (mean MDFI 3.82 vs 7.25; P = 0.021), which was accompanied by an increase of IL-6, could be observed.
248	12483990	The comparison of mature DCs (Day 10) between patients and controls indicated no significant differences, except for CD83 (mean MDFI 1.7 vs 1.5; P = 0.042) and CD80 (mean MDFI 15.92 vs 12.73; P = 0.042).
249	12520519	Dendritic cells (DCs) not only induce but also modulate T cell activation. 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] induces DCs with a tolerogenic phenotype, characterized by decreased expression of CD40, CD80, and CD86 costimulatory molecules, low IL-12 and enhanced IL-10 secretion.
250	12520519	The enhancement of CD4(+)CD25(+) regulatory T cells, able to mediate transplantation tolerance and to arrest type 1 diabetes development by a short oral treatment with VDR ligands, suggests possible clinical applications of this approach.
251	12538715	FcR-binding "classical" anti-CD3 mAb is a potent immunosuppressive drug that alters CD4(+) and CD8(+) T cell function in vivo via anergy induction and programmed cell death (PCD).
252	12538715	Anti-CD3-mediated PCD was Fas independent but was mediated by the mitochondria-initiated apoptosis that was abrogated in Bcl-x(L)-transgenic T cells.
253	12538715	The PCD was more pronounced in CD28-deficient mice consistent with defective Bcl-x(L) up-regulation.
254	12538715	Residual T cells isolated from anti-CD3-treated wild-type, CD28(-/-), and Bcl-x(L)-transgenic mice were hyporesponsive.
255	12538715	The hyporesponsiveness was more pronounced in CD28(-/-) and wild-type mice treated with anti-B7-2, suggesting that CD28 interaction with B7-2 regulates T cell responsiveness in anti-CD3-treated animals.
256	12573055	DC infected with any of the Ad vectors expressed higher levels of CD40, CD80, and CD86 molecules than uninfected DC and Ad.IL-4 DC produced IL-4 after lipopolysaccharide (LPS) and interferon (IFN)-gamma stimulation.
257	12573055	Ad-infected DC efficiently stimulated allogeneic T cells, and cultures of T cells with Ad.IL-4 DC produced lower levels of IFN-gamma and marginally higher levels of IL-4.
258	12573055	The intrapancreatic IFN-gamma:IL-4 or IFN-gamma:IL-10 cytokine ratios were lower in 10-week-old mice treated with Ad.IL-4 DC, and these mice were significantly protected from disease.
259	12724780	Here we identify polymorphisms of the cytotoxic T lymphocyte antigen 4 gene (CTLA4)--which encodes a vital negative regulatory molecule of the immune system--as candidates for primary determinants of risk of the common autoimmune disorders Graves' disease, autoimmune hypothyroidism and type 1 diabetes.
260	12724780	In the mouse model of type 1 diabetes, susceptibility was also associated with variation in CTLA-4 gene splicing with reduced production of a splice form encoding a molecule lacking the CD80/CD86 ligand-binding domain.
261	12727648	Dendritic cells (DCs) not only induce but also modulate T cell activation. 1,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] induces DCs with a tolerogenic phenotype, characterized by decreased expression of CD40, CD80, and CD86 co-stimulatory molecules, low IL-12, and enhanced IL-10 secretion.
262	12727648	Graft acceptance is associated with impaired development of type 1 CD4(+) and CD8(+) cells and an increased percentage of CD4(+)CD25(+) regulatory cells expressing CD152 in the spleen and in the draining lymph node.
263	12727648	CD4(+)CD25(+) cells that are able to inhibit the T cell response to a pancreatic autoantigen and to significantly delay disease transfer by pathogenic CD4(+)CD25(-) cells are also induced by treatment of adult nonobese diabetic (NOD) mice with a selected vitamin D receptor (VDR) ligand.
264	12727648	The enhancement of CD4(+)CD25(+) regulatory T cells able to mediate transplantation tolerance and to arrest type 1 diabetes development by a short oral treatment with small organic compounds that induce tolerogenic DCs, like VDR ligands, suggests possible clinical applications of this approach.
265	12742378	We have recently described an impaired proliferative response of CD4(+) T-cells to primary antigens in patients with insulin-dependent diabetes mellitus (IDDM) [Clin.
266	12742378	In order to further investigate possible mechanisms underlying this impairment, several factors known to be involved in the down-regulation of the immune response both at the level of APCs and CD4(+) T-cells were investigated: Monocyte-derived dendritic cells (MDDC) from IDDM patients were shown to express elevated amounts of CD86 (B7.2) (p=0.003) and reduced amounts of the adhesion molecule CD54 (ICAM-1) (p=0.03) on their cell surface compared to age-matched healthy controls and patients with non-insulin-dependent diabetes mellitus (NIDDM) as well as decreased SDS-PAGE stability of HLA-DQ and -DR peptide complexes directly isolated from the IDDM patients' peripheral blood mononuclear cells (PBMCs).
267	12742378	Expression of CTLA-4 (CD152), known to be involved in the down-regulation of the immune response, was shown to be increased on CD4(+) T-cells from IDDM patients after exposure to the primary antigen KLH (keyhole limpet hemocyanin) presented by MDDC (p=0.0047).
268	12742378	Likewise, purified CD4(+) T-cells from IDDM patients produced elevated levels of the cytokine TGF-beta1 after stimulation with immobilized monoclonal antibodies directed against CD3 and CD28 (p=0.014).
269	12742378	When monocytes from IDDM patients were stimulated with lipopolysaccharide (LPS), an increased tendency to produce the inhibitory cytokine interleukin (IL)-10 (p=0.007) and the acute phase cytokine IL-6 (p=0.044) was observed, whereas the concentrations of tumor necrosis factor (TNF)-alpha, IL-1beta, and IL-12 were comparable to controls.
270	14634066	Expression of CD11c, CD40, CD54, and major histocompatibility complex I-A(g7) was reduced in cells cultured with additional DcR3.Fc, compared with DCs incubated with granulocyte macrophage-colony stimulating factor and interleukin (IL)-4, indicating that DcR3 interferes with the differentiation and maturation of BM-DCs.
271	14634066	One of the most striking effects of DcR3.Fc on the differentiation of DCs was the up-regulation of CD86 and down-regulation of CD80, suggesting a modulatory potential to skew the T cell response toward the T helper cell type 2 (Th2) phenotype.
272	14634066	Moreover, the secretion of interferon-gamma from T cells cocultured with DcR3.Fc-treated DCs was profoundly suppressed, indicating that DcR3 exerts a Th1-suppressing effect on differentiating DCs.
273	14634066	Data from two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight analysis show an up-regulation of some proteins-such as mitogen-activated protein kinase p38 beta, cyclin-dependent kinase 6, and signal-induced proliferation-associated gene 1-and a down-regulation of the IL-17 precursor; tumor necrosis factor-related apoptosis-inducing ligand family member-associated nuclear factor-kappaB activator-binding kinase 1; and Golgi S-nitroso-N-acetylpenicillamine in cells treated with DcR3, further demonstrating its effect on DC differentiation and function.
274	14634096	Systemic and pancreatic cytokine profiles deviated to a Th1-dominant state, and the the frequency of glutamic acid decarboxylase-reactive IFN-gamma-producing CD4(+) cells was also high in the IL-18 group.
275	14634096	Moreover, it was suggested that the promoting effect of IL-18 might be associated with increased peripheral IL-12, CD86, and pancreatic IFN-inducible protein-10 mRNA expression levels.
276	15142525	This splice variant of CTLA-4, named ligand-independent CTLA-4 (liCTLA-4), lacks exon2 including the MYPPPY motif essential for binding to the costimulatory ligands B7-1 and B7-2.
277	15194405	Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.
278	15194405	The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established.
279	15194405	Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection.
280	15194405	However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown.
281	15194405	The purpose of this study was to determine whether islet allografts and/or rat islet xenografts required host CD80/CD86 molecules for acute rejection.
282	15194405	Streptozotocin-induced diabetic C57Bl/6 (B6, H-2(b)) or B6 CD80/CD86 double-deficient mice were grafted with allogeneic BALB/c (H-2(d)) islet allografts or with WF (RT1(u)) islet xenografts.
283	15194405	Consistent with previous reports, BALB/c islet allografts were acutely rejected in wild-type B6 mice could survive long-term (>100 days) in B6 CD80/CD86-deficient animals.
284	15194405	In stark contrast, both islet allografts and WF rat islet xenografts demonstrated acute rejection in both control B6 and in B6 CD80/CD86 deficient hosts.
285	15194405	The present study illustrates this concept by showing a marked difference in the role of host-derived CD80/CD86 costimulatory molecules for cardiac allograft versus islet allograft/xenograft rejection in vivo.
286	15194405	Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.
287	15194405	The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established.
288	15194405	Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection.
289	15194405	However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown.
290	15194405	The purpose of this study was to determine whether islet allografts and/or rat islet xenografts required host CD80/CD86 molecules for acute rejection.
291	15194405	Streptozotocin-induced diabetic C57Bl/6 (B6, H-2(b)) or B6 CD80/CD86 double-deficient mice were grafted with allogeneic BALB/c (H-2(d)) islet allografts or with WF (RT1(u)) islet xenografts.
292	15194405	Consistent with previous reports, BALB/c islet allografts were acutely rejected in wild-type B6 mice could survive long-term (>100 days) in B6 CD80/CD86-deficient animals.
293	15194405	In stark contrast, both islet allografts and WF rat islet xenografts demonstrated acute rejection in both control B6 and in B6 CD80/CD86 deficient hosts.
294	15194405	The present study illustrates this concept by showing a marked difference in the role of host-derived CD80/CD86 costimulatory molecules for cardiac allograft versus islet allograft/xenograft rejection in vivo.
295	15194405	Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.
296	15194405	The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established.
297	15194405	Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection.
298	15194405	However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown.
299	15194405	The purpose of this study was to determine whether islet allografts and/or rat islet xenografts required host CD80/CD86 molecules for acute rejection.
300	15194405	Streptozotocin-induced diabetic C57Bl/6 (B6, H-2(b)) or B6 CD80/CD86 double-deficient mice were grafted with allogeneic BALB/c (H-2(d)) islet allografts or with WF (RT1(u)) islet xenografts.
301	15194405	Consistent with previous reports, BALB/c islet allografts were acutely rejected in wild-type B6 mice could survive long-term (>100 days) in B6 CD80/CD86-deficient animals.
302	15194405	In stark contrast, both islet allografts and WF rat islet xenografts demonstrated acute rejection in both control B6 and in B6 CD80/CD86 deficient hosts.
303	15194405	The present study illustrates this concept by showing a marked difference in the role of host-derived CD80/CD86 costimulatory molecules for cardiac allograft versus islet allograft/xenograft rejection in vivo.
304	15194405	Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.
305	15194405	The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established.
306	15194405	Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection.
307	15194405	However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown.
308	15194405	The purpose of this study was to determine whether islet allografts and/or rat islet xenografts required host CD80/CD86 molecules for acute rejection.
309	15194405	Streptozotocin-induced diabetic C57Bl/6 (B6, H-2(b)) or B6 CD80/CD86 double-deficient mice were grafted with allogeneic BALB/c (H-2(d)) islet allografts or with WF (RT1(u)) islet xenografts.
310	15194405	Consistent with previous reports, BALB/c islet allografts were acutely rejected in wild-type B6 mice could survive long-term (>100 days) in B6 CD80/CD86-deficient animals.
311	15194405	In stark contrast, both islet allografts and WF rat islet xenografts demonstrated acute rejection in both control B6 and in B6 CD80/CD86 deficient hosts.
312	15194405	The present study illustrates this concept by showing a marked difference in the role of host-derived CD80/CD86 costimulatory molecules for cardiac allograft versus islet allograft/xenograft rejection in vivo.
313	15194405	Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.
314	15194405	The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established.
315	15194405	Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection.
316	15194405	However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown.
317	15194405	The purpose of this study was to determine whether islet allografts and/or rat islet xenografts required host CD80/CD86 molecules for acute rejection.
318	15194405	Streptozotocin-induced diabetic C57Bl/6 (B6, H-2(b)) or B6 CD80/CD86 double-deficient mice were grafted with allogeneic BALB/c (H-2(d)) islet allografts or with WF (RT1(u)) islet xenografts.
319	15194405	Consistent with previous reports, BALB/c islet allografts were acutely rejected in wild-type B6 mice could survive long-term (>100 days) in B6 CD80/CD86-deficient animals.
320	15194405	In stark contrast, both islet allografts and WF rat islet xenografts demonstrated acute rejection in both control B6 and in B6 CD80/CD86 deficient hosts.
321	15194405	The present study illustrates this concept by showing a marked difference in the role of host-derived CD80/CD86 costimulatory molecules for cardiac allograft versus islet allograft/xenograft rejection in vivo.
322	15194405	Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.
323	15194405	The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established.
324	15194405	Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection.
325	15194405	However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown.
326	15194405	The purpose of this study was to determine whether islet allografts and/or rat islet xenografts required host CD80/CD86 molecules for acute rejection.
327	15194405	Streptozotocin-induced diabetic C57Bl/6 (B6, H-2(b)) or B6 CD80/CD86 double-deficient mice were grafted with allogeneic BALB/c (H-2(d)) islet allografts or with WF (RT1(u)) islet xenografts.
328	15194405	Consistent with previous reports, BALB/c islet allografts were acutely rejected in wild-type B6 mice could survive long-term (>100 days) in B6 CD80/CD86-deficient animals.
329	15194405	In stark contrast, both islet allografts and WF rat islet xenografts demonstrated acute rejection in both control B6 and in B6 CD80/CD86 deficient hosts.
330	15194405	The present study illustrates this concept by showing a marked difference in the role of host-derived CD80/CD86 costimulatory molecules for cardiac allograft versus islet allograft/xenograft rejection in vivo.
331	15194405	Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.
332	15194405	The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established.
333	15194405	Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection.
334	15194405	However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown.
335	15194405	The purpose of this study was to determine whether islet allografts and/or rat islet xenografts required host CD80/CD86 molecules for acute rejection.
336	15194405	Streptozotocin-induced diabetic C57Bl/6 (B6, H-2(b)) or B6 CD80/CD86 double-deficient mice were grafted with allogeneic BALB/c (H-2(d)) islet allografts or with WF (RT1(u)) islet xenografts.
337	15194405	Consistent with previous reports, BALB/c islet allografts were acutely rejected in wild-type B6 mice could survive long-term (>100 days) in B6 CD80/CD86-deficient animals.
338	15194405	In stark contrast, both islet allografts and WF rat islet xenografts demonstrated acute rejection in both control B6 and in B6 CD80/CD86 deficient hosts.
339	15194405	The present study illustrates this concept by showing a marked difference in the role of host-derived CD80/CD86 costimulatory molecules for cardiac allograft versus islet allograft/xenograft rejection in vivo.
340	15194405	Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.
341	15194405	The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established.
342	15194405	Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection.
343	15194405	However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown.
344	15194405	The purpose of this study was to determine whether islet allografts and/or rat islet xenografts required host CD80/CD86 molecules for acute rejection.
345	15194405	Streptozotocin-induced diabetic C57Bl/6 (B6, H-2(b)) or B6 CD80/CD86 double-deficient mice were grafted with allogeneic BALB/c (H-2(d)) islet allografts or with WF (RT1(u)) islet xenografts.
346	15194405	Consistent with previous reports, BALB/c islet allografts were acutely rejected in wild-type B6 mice could survive long-term (>100 days) in B6 CD80/CD86-deficient animals.
347	15194405	In stark contrast, both islet allografts and WF rat islet xenografts demonstrated acute rejection in both control B6 and in B6 CD80/CD86 deficient hosts.
348	15194405	The present study illustrates this concept by showing a marked difference in the role of host-derived CD80/CD86 costimulatory molecules for cardiac allograft versus islet allograft/xenograft rejection in vivo.
349	15194405	Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.
350	15194405	The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established.
351	15194405	Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection.
352	15194405	However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown.
353	15194405	The purpose of this study was to determine whether islet allografts and/or rat islet xenografts required host CD80/CD86 molecules for acute rejection.
354	15194405	Streptozotocin-induced diabetic C57Bl/6 (B6, H-2(b)) or B6 CD80/CD86 double-deficient mice were grafted with allogeneic BALB/c (H-2(d)) islet allografts or with WF (RT1(u)) islet xenografts.
355	15194405	Consistent with previous reports, BALB/c islet allografts were acutely rejected in wild-type B6 mice could survive long-term (>100 days) in B6 CD80/CD86-deficient animals.
356	15194405	In stark contrast, both islet allografts and WF rat islet xenografts demonstrated acute rejection in both control B6 and in B6 CD80/CD86 deficient hosts.
357	15194405	The present study illustrates this concept by showing a marked difference in the role of host-derived CD80/CD86 costimulatory molecules for cardiac allograft versus islet allograft/xenograft rejection in vivo.
358	15225820	After culture with 20 ng/ml GM-CSF + 20 ng/ml IL-4 (8 days) followed by 1000 ng/ml LPS + 100 U/ml IFN-gamma (2 days), with or without 10(-8)M TX527, cells were counted and analyzed by FACS for MHC II, CD86, CD40 and CD54 expression within the CD11c(+) DC population.
359	15225820	On CD11c(+) DCs, MHC II, CD86 and CD54 were significantly down-regulated and CD40 was twofold upregulated.
360	15225820	After culture with 20 ng/ml GM-CSF + 20 ng/ml IL-4 (8 days) followed by 1000 ng/ml LPS + 100 U/ml IFN-gamma (2 days), with or without 10(-8)M TX527, cells were counted and analyzed by FACS for MHC II, CD86, CD40 and CD54 expression within the CD11c(+) DC population.
361	15225820	On CD11c(+) DCs, MHC II, CD86 and CD54 were significantly down-regulated and CD40 was twofold upregulated.
362	15265926	This induced DC maturation as estimated by all surface markers tested (MHC class II, CD40, CD54, and CD86).
363	15293882	Surfactant protein A (SP-A) is a lung collectin with diverse immunoregulatory activities.
364	15293882	Bone marrow-derived DCs generated in the presence of SP-A fail to increase lipopolysaccharide-induced upregulation of major histocompatibility complex (MHC) class II and CD86 costimulatory molecule on DCs surface and behaves like "tolerogenic DCs".
365	15356107	B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets.
366	15356107	We investigated the role played by B7-2 in influencing pathogenic autoimmunity from islet-reactive CD4 T cells in B7-2 knockout (KO) NOD mice which are protected from type 1 diabetes.
367	15356107	B7-2 deficiency caused a profound diminishment in the generation of spontaneously activated CD4 T cells and islet-specific CD4 T cell expansion.
368	15356107	CD4 T cells showed some hallmarks of hyporesponsiveness because TCR/CD28-mediated stimulation led to defective activation and failure to induce disease in NODscid recipients.
369	15356107	Furthermore, CD4 T cells exhibited enhanced death in the absence of B7-2.
370	15356107	Interestingly, we found that B7-2 is required to achieve normal levels of CD4+CD25+CD62L+ T regulatory cells because a significant reduction of these T regulatory cells was observed in the thymus but not in the peripheral compartments of B7-2KO mice.
371	15356107	Taken together these results clearly indicate that B7-2 plays a critical role in priming islet-reactive CD4 T cells, suggesting a simplified, two-cell model for the impact of this costimulatory molecule in autoimmunity against islets.
372	15356107	B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets.
373	15356107	We investigated the role played by B7-2 in influencing pathogenic autoimmunity from islet-reactive CD4 T cells in B7-2 knockout (KO) NOD mice which are protected from type 1 diabetes.
374	15356107	B7-2 deficiency caused a profound diminishment in the generation of spontaneously activated CD4 T cells and islet-specific CD4 T cell expansion.
375	15356107	CD4 T cells showed some hallmarks of hyporesponsiveness because TCR/CD28-mediated stimulation led to defective activation and failure to induce disease in NODscid recipients.
376	15356107	Furthermore, CD4 T cells exhibited enhanced death in the absence of B7-2.
377	15356107	Interestingly, we found that B7-2 is required to achieve normal levels of CD4+CD25+CD62L+ T regulatory cells because a significant reduction of these T regulatory cells was observed in the thymus but not in the peripheral compartments of B7-2KO mice.
378	15356107	Taken together these results clearly indicate that B7-2 plays a critical role in priming islet-reactive CD4 T cells, suggesting a simplified, two-cell model for the impact of this costimulatory molecule in autoimmunity against islets.
379	15356107	B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets.
380	15356107	We investigated the role played by B7-2 in influencing pathogenic autoimmunity from islet-reactive CD4 T cells in B7-2 knockout (KO) NOD mice which are protected from type 1 diabetes.
381	15356107	B7-2 deficiency caused a profound diminishment in the generation of spontaneously activated CD4 T cells and islet-specific CD4 T cell expansion.
382	15356107	CD4 T cells showed some hallmarks of hyporesponsiveness because TCR/CD28-mediated stimulation led to defective activation and failure to induce disease in NODscid recipients.
383	15356107	Furthermore, CD4 T cells exhibited enhanced death in the absence of B7-2.
384	15356107	Interestingly, we found that B7-2 is required to achieve normal levels of CD4+CD25+CD62L+ T regulatory cells because a significant reduction of these T regulatory cells was observed in the thymus but not in the peripheral compartments of B7-2KO mice.
385	15356107	Taken together these results clearly indicate that B7-2 plays a critical role in priming islet-reactive CD4 T cells, suggesting a simplified, two-cell model for the impact of this costimulatory molecule in autoimmunity against islets.
386	15356107	B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets.
387	15356107	We investigated the role played by B7-2 in influencing pathogenic autoimmunity from islet-reactive CD4 T cells in B7-2 knockout (KO) NOD mice which are protected from type 1 diabetes.
388	15356107	B7-2 deficiency caused a profound diminishment in the generation of spontaneously activated CD4 T cells and islet-specific CD4 T cell expansion.
389	15356107	CD4 T cells showed some hallmarks of hyporesponsiveness because TCR/CD28-mediated stimulation led to defective activation and failure to induce disease in NODscid recipients.
390	15356107	Furthermore, CD4 T cells exhibited enhanced death in the absence of B7-2.
391	15356107	Interestingly, we found that B7-2 is required to achieve normal levels of CD4+CD25+CD62L+ T regulatory cells because a significant reduction of these T regulatory cells was observed in the thymus but not in the peripheral compartments of B7-2KO mice.
392	15356107	Taken together these results clearly indicate that B7-2 plays a critical role in priming islet-reactive CD4 T cells, suggesting a simplified, two-cell model for the impact of this costimulatory molecule in autoimmunity against islets.
393	15356107	B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets.
394	15356107	We investigated the role played by B7-2 in influencing pathogenic autoimmunity from islet-reactive CD4 T cells in B7-2 knockout (KO) NOD mice which are protected from type 1 diabetes.
395	15356107	B7-2 deficiency caused a profound diminishment in the generation of spontaneously activated CD4 T cells and islet-specific CD4 T cell expansion.
396	15356107	CD4 T cells showed some hallmarks of hyporesponsiveness because TCR/CD28-mediated stimulation led to defective activation and failure to induce disease in NODscid recipients.
397	15356107	Furthermore, CD4 T cells exhibited enhanced death in the absence of B7-2.
398	15356107	Interestingly, we found that B7-2 is required to achieve normal levels of CD4+CD25+CD62L+ T regulatory cells because a significant reduction of these T regulatory cells was observed in the thymus but not in the peripheral compartments of B7-2KO mice.
399	15356107	Taken together these results clearly indicate that B7-2 plays a critical role in priming islet-reactive CD4 T cells, suggesting a simplified, two-cell model for the impact of this costimulatory molecule in autoimmunity against islets.
400	15356107	B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets.
401	15356107	We investigated the role played by B7-2 in influencing pathogenic autoimmunity from islet-reactive CD4 T cells in B7-2 knockout (KO) NOD mice which are protected from type 1 diabetes.
402	15356107	B7-2 deficiency caused a profound diminishment in the generation of spontaneously activated CD4 T cells and islet-specific CD4 T cell expansion.
403	15356107	CD4 T cells showed some hallmarks of hyporesponsiveness because TCR/CD28-mediated stimulation led to defective activation and failure to induce disease in NODscid recipients.
404	15356107	Furthermore, CD4 T cells exhibited enhanced death in the absence of B7-2.
405	15356107	Interestingly, we found that B7-2 is required to achieve normal levels of CD4+CD25+CD62L+ T regulatory cells because a significant reduction of these T regulatory cells was observed in the thymus but not in the peripheral compartments of B7-2KO mice.
406	15356107	Taken together these results clearly indicate that B7-2 plays a critical role in priming islet-reactive CD4 T cells, suggesting a simplified, two-cell model for the impact of this costimulatory molecule in autoimmunity against islets.
407	15383562	Phenotypically "immature" dendritic cells (DCs), defined by low cell surface CD40, CD80, and CD86 can elicit host immune suppression in allotransplantation and autoimmunity.
408	15383562	CD40, CD80, and CD86 cell surface molecules were specifically down-regulated by treating NOD DCs ex vivo with a mixture of antisense oligonucleotides targeting the CD40, CD80, and CD86 primary transcripts.
409	15383562	Engineered DC promoted an increased prevalence of CD4(+)CD25(+) T cells in NOD recipients at all ages examined and diabetes-free recipients exhibited significantly greater numbers of CD4(+)CD25(+) T cells compared with untreated NOD mice.
410	15383562	Phenotypically "immature" dendritic cells (DCs), defined by low cell surface CD40, CD80, and CD86 can elicit host immune suppression in allotransplantation and autoimmunity.
411	15383562	CD40, CD80, and CD86 cell surface molecules were specifically down-regulated by treating NOD DCs ex vivo with a mixture of antisense oligonucleotides targeting the CD40, CD80, and CD86 primary transcripts.
412	15383562	Engineered DC promoted an increased prevalence of CD4(+)CD25(+) T cells in NOD recipients at all ages examined and diabetes-free recipients exhibited significantly greater numbers of CD4(+)CD25(+) T cells compared with untreated NOD mice.
413	15634886	An age-dependent differential expression of B7-1 and B7-2 was associated with the development of insulitis and CD4(+)CD25(+) T cell deficiency in autoimmune disease-prone mice.
414	15634886	Whereas BCR and LPS stimulation increased B7-2 expression on B cells from autoimmune disease-prone and nonautoimmune disease-prone mice, LPS-induced B7-1 expression was higher on NOD than C57BL/6 B cells.
415	15634886	B7 blockade of BCR-stimulated NOD B cells by anti-B7-1 and anti-B7-2 mAbs during coadoptive transfer with diabetogenic T cells into NOD.scid mice protected these recipients from T1D.
416	15634886	An age-dependent differential expression of B7-1 and B7-2 was associated with the development of insulitis and CD4(+)CD25(+) T cell deficiency in autoimmune disease-prone mice.
417	15634886	Whereas BCR and LPS stimulation increased B7-2 expression on B cells from autoimmune disease-prone and nonautoimmune disease-prone mice, LPS-induced B7-1 expression was higher on NOD than C57BL/6 B cells.
418	15634886	B7 blockade of BCR-stimulated NOD B cells by anti-B7-1 and anti-B7-2 mAbs during coadoptive transfer with diabetogenic T cells into NOD.scid mice protected these recipients from T1D.
419	15634886	An age-dependent differential expression of B7-1 and B7-2 was associated with the development of insulitis and CD4(+)CD25(+) T cell deficiency in autoimmune disease-prone mice.
420	15634886	Whereas BCR and LPS stimulation increased B7-2 expression on B cells from autoimmune disease-prone and nonautoimmune disease-prone mice, LPS-induced B7-1 expression was higher on NOD than C57BL/6 B cells.
421	15634886	B7 blockade of BCR-stimulated NOD B cells by anti-B7-1 and anti-B7-2 mAbs during coadoptive transfer with diabetogenic T cells into NOD.scid mice protected these recipients from T1D.
422	15677501	Bone marrow (BM) was cultured in granulocyte macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta1, a cytokine combination that expands myeloid cells but inhibits terminal DC differentiation, to yield Gr-1(+)/CD11b(+)/CD11c(-) myeloid progenitor cells and a minor population of CD11c(+)/CD11b(+)/CD86(lo) immature DCs.
423	15677501	After transfer, Gr-1(+) myeloid cells acquired the characteristics of resting DCs (CD11c(+)/MHC classII(int)/CD86(lo)/CD40(lo)).
424	15677501	Gr-1(+) myeloid cells generated from transgenic NOD mice that expressed proinsulin controlled by a major histocompatibility complex (MHC) class II promoter, but not from wild-type NOD mice, transferred into 4-week-old female NOD mice significantly suppressed diabetes development.
425	15677501	Bone marrow (BM) was cultured in granulocyte macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta1, a cytokine combination that expands myeloid cells but inhibits terminal DC differentiation, to yield Gr-1(+)/CD11b(+)/CD11c(-) myeloid progenitor cells and a minor population of CD11c(+)/CD11b(+)/CD86(lo) immature DCs.
426	15677501	After transfer, Gr-1(+) myeloid cells acquired the characteristics of resting DCs (CD11c(+)/MHC classII(int)/CD86(lo)/CD40(lo)).
427	15677501	Gr-1(+) myeloid cells generated from transgenic NOD mice that expressed proinsulin controlled by a major histocompatibility complex (MHC) class II promoter, but not from wild-type NOD mice, transferred into 4-week-old female NOD mice significantly suppressed diabetes development.
428	15699515	Surface expression of MHC II, CD86, and CD54 on NOR-derived DCs was decreased after 1,25(OH)(2)D(3) treatment, while CD40 remained unchanged.
429	15699515	On NOD-derived DCs, 1,25(OH)(2)D(3) only inhibited the expression of MHC II and CD86. 1,25(OH)(2)D(3) inhibited IL-12 and IL-10 secretion after IFNgamma and LPS stimulation.
430	15699515	Surface expression of MHC II, CD86, and CD54 on NOR-derived DCs was decreased after 1,25(OH)(2)D(3) treatment, while CD40 remained unchanged.
431	15699515	On NOD-derived DCs, 1,25(OH)(2)D(3) only inhibited the expression of MHC II and CD86. 1,25(OH)(2)D(3) inhibited IL-12 and IL-10 secretion after IFNgamma and LPS stimulation.
432	15972645	CTLA-4 binding to B7-1/B7-2 is believed to be crucial for its inhibitory signal both by competing for CD28 binding to the same ligands and aggregating CTLA-4 to deliver negative signals.
433	15999808	This splice variant of CTLA4, named ligand-independent CTLA4 (liCTLA4), lacks exon 2 including the MYPPPY motif essential for binding to the costimulatory ligands B7-1 and B7-2. liCTLA4 is expressed as a protein in primary T cells and strongly inhibits T cell responses by binding and dephosphorylating the TcRzeta chain.
434	16232222	Mature DC (mDC) from 18 children with T1DM and 10 age-matched healthy children were tested. mDC, derived from peripheral blood monocytes cultured for 6 days in presence of interleukin (IL)-4 and granulocyte-macrophage colony stimulating factor (GM-CSF) and stimulated with lipopolysaccharide (LPS) for the last 24 h, were phenotyped for the expression of the co-stimulatory molecules B7.1 and B7.2.
435	16232222	We also measured IL-10 and IL-12 concentration in the supernatant of DC cultures.
436	16232222	Interestingly, we observed in the patients a sevenfold higher level of IL-10 (P = 0.07) and a ninefold lower level of IL-12 (P = 0.01).
437	16380489	Interleukin-7 is a survival factor for CD4+ CD25+ T-cells and is expressed by diabetes-suppressive dendritic cells.
438	16380489	Recent studies demonstrate that immunoregulatory dendritic cells (iDCs) confer immune hyporesponsiveness in part through CD4(+) CD25(+) T regulatory cells (Tregs).
439	16380489	Herein, we provide evidence to support the hypothesis that dendritic cells derived from NOD mice and engineered ex vivo to exhibit suppressed expression of the CD40, CD80, and CD86 costimulatory molecules motivate an increase in the prevalence of regulatory CD4(+) CD25(+) T-cells via interleukin (IL)-7.
440	16380489	Exogenous addition of IL-7 to NOD T-cells did not promote expansion or proliferation, but instead selectively maintained the number of CD4(+) CD25(+) T-cells by inhibiting activation of apoptosis in these cells.
441	16380489	In vitro, IL-7 receptor alpha-chain (IL-7Ralpha) was expressed at significantly higher levels on CD4(+) CD25(+) T-cells compared with CD4(+) CD25(-) T-cells irrespective of resting or stimulated state.
442	16380489	In vivo, CD4(+) CD25(+) T-cells obtained from NOD-scid mice reconstituted with ex vivo engineered iDCs and NOD splenocytes expressed significantly higher levels of IL-7Ralpha compared with levels in the CD4(+) CD25(-) subset, especially in diabetes-suppressive dendritic cell-administered NOD-scid recipients.
443	16380489	Taken together, our data suggest a novel mechanism by which iDCs delay autoimmunity through the CD4(+) CD25(+) Treg pathway and suggest IL-7 as a survival factor for these putative Tregs, which express the alpha-chain of its receptor at considerably higher levels than CD4(+) CD25(-) T-cells.
444	16886063	However, it has been difficult to explore the biology of selective engagement of CTLA-4 in vivo because CTLA-4 shares its ligands, B7-1 and B7-2, with CD28.
445	16886063	Finally, this disease prevention occurred in Treg-deficient NOD.B7-1/B7-2 double-knockout mice, suggesting that the effect of the CTLA-4 agonist directly attenuates autoreactive T cell activation, not Treg activation.
446	16886063	However, it has been difficult to explore the biology of selective engagement of CTLA-4 in vivo because CTLA-4 shares its ligands, B7-1 and B7-2, with CD28.
447	16886063	Finally, this disease prevention occurred in Treg-deficient NOD.B7-1/B7-2 double-knockout mice, suggesting that the effect of the CTLA-4 agonist directly attenuates autoreactive T cell activation, not Treg activation.
448	17202352	Successful Ag activation of naive T helper cells requires at least two signals consisting of TCR and CD28 on the T cell interacting with MHC II and CD80/CD86, respectively, on APCs.
449	17202352	We have reported that modulation of redox balance with a catalytic antioxidant effectively inhibited the generation of third signal components from the innate immune response (TNF-alpha, IL-1beta, ROS).
450	17202352	Modulating redox balance led to decreased Ag-specific T cell proliferation and IFN-gamma synthesis by diminishing ROS production in the APC, which affected TNF-alpha levels produced by CD4(+) T cells and impairing effector function.
451	17243007	Immunomodulation of the anti-islet CD8 T cell response by B7-2.
452	17243007	We asked whether the CD8 T cell compartment is impacted by the absence of B7-2.
453	17243007	Adoptive transfer experiments using in vitro activated anti-islet CD8 T cells showed that B7-2 does not control the effector phase of the autoreactive CD8 T cell response.
454	17243007	Our data indicate that B7-2 promotes pancreatic autoimmunity by controlling CD8 T cell expansion and effector function, but is dispensable for CD8 T cell activation, survival, and the effector phase of anti-islet CD8 T cell response.
455	17243007	Immunomodulation of the anti-islet CD8 T cell response by B7-2.
456	17243007	We asked whether the CD8 T cell compartment is impacted by the absence of B7-2.
457	17243007	Adoptive transfer experiments using in vitro activated anti-islet CD8 T cells showed that B7-2 does not control the effector phase of the autoreactive CD8 T cell response.
458	17243007	Our data indicate that B7-2 promotes pancreatic autoimmunity by controlling CD8 T cell expansion and effector function, but is dispensable for CD8 T cell activation, survival, and the effector phase of anti-islet CD8 T cell response.
459	17243007	Immunomodulation of the anti-islet CD8 T cell response by B7-2.
460	17243007	We asked whether the CD8 T cell compartment is impacted by the absence of B7-2.
461	17243007	Adoptive transfer experiments using in vitro activated anti-islet CD8 T cells showed that B7-2 does not control the effector phase of the autoreactive CD8 T cell response.
462	17243007	Our data indicate that B7-2 promotes pancreatic autoimmunity by controlling CD8 T cell expansion and effector function, but is dispensable for CD8 T cell activation, survival, and the effector phase of anti-islet CD8 T cell response.
463	17243007	Immunomodulation of the anti-islet CD8 T cell response by B7-2.
464	17243007	We asked whether the CD8 T cell compartment is impacted by the absence of B7-2.
465	17243007	Adoptive transfer experiments using in vitro activated anti-islet CD8 T cells showed that B7-2 does not control the effector phase of the autoreactive CD8 T cell response.
466	17243007	Our data indicate that B7-2 promotes pancreatic autoimmunity by controlling CD8 T cell expansion and effector function, but is dispensable for CD8 T cell activation, survival, and the effector phase of anti-islet CD8 T cell response.
467	17430175	The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two neuropeptides belonging to the VIP/secretin/glucagon family of peptides.
468	17430175	In addition, VIP/PACAP reduce the expression of costimulatory molecules (particularly CD80 and CD86) on the antigen-presenting cells, and therefore reduce stimulation of antigen-specific CD4(+) T cells.
469	17462956	The decrease in MDC and PDC counts was less evident in patients with a combination of T1D and coeliac disease (CD) or CD alone.
470	17462956	The age-dependent decline in blood DC numbers, found in control children, was not evident in ND patients, such that 2-10 years old ND children had similar MDC and PDC numbers to 15-17 years old controls.
471	17462956	In ED patients the t-score of MDC and PDC numbers related to the age of diagnosis but not to disease duration.
472	17462956	Blood DC in T1D patients were not distinguished from those of controls by the levels of HLA-DR, CD40 and CD86 expression or the percentage of DC expressing cytokines, IL-12, IL-10, IL-6 and TNF-alpha, in responses to poly I:C.
473	17785799	Granulocyte-macrophage colony-stimulating factor prevents diabetes development in NOD mice by inducing tolerogenic dendritic cells that sustain the suppressive function of CD4+CD25+ regulatory T cells.
474	17785799	The protection was associated with a marked increase in the number of tolerogenic immature splenic DCs and in the number of Foxp3+CD4+CD25+ regulatory T cells (Tregs).
475	17785799	Activated DCs from GM-CSF-protected mice expressed lower levels of MHC class II and CD80/CD86 molecules, produced more IL-10 and were less effective in stimulating diabetogenic CD8+ T cells than DCs of PBS-treated NOD mice.
476	17785799	Depletion of CD11c+ DCs before transfer released diabetogenic T cells from the suppressive effect of CD4+CD25+ Tregs, thereby promoting the development of diabetes.
477	17785799	These results indicated that semimature DCs were required for the sustained suppressive function of CD4+CD25+ Tregs that were responsible for maintaining tolerance of diabetogenic T cells in NOD mice.
478	17924973	Cytotoxic T lymphocyte antigen 4 (CTLA4) is a potent inhibitory co-stimulatory molecule believed to be involved in type 1 diabetes and other autoimmune diseases.
479	17924973	All three CTLA4 molecules were able to bind to antigen-presenting cells and inhibit the expression of CD80/CD86. sCTLA4 was able to suppress proliferation of different committed autoreactive T cell clones in a dose-dependent manner, whereas CTLA4Ig and LEA29Y were not.
480	17947667	CD86 has sustained costimulatory effects on CD8 T cells.
481	17947667	CD80 and CD86 both costimulate T cell activation.
482	17947667	We have studied mice expressing rat insulin promoter (RIP)-CD80 and RIP-CD86 on the NOD and NOD.scid genetic background to generate in vivo models, using diabetes as a readout for cytotoxic T cell activation.
483	17947667	However, the secondary in vivo response was maintained if T cells were activated through CD86 costimulation compared with CD80.
484	17947667	In vitro, CD80 costimulation enhanced cytotoxicity, proliferation, and cytokine secretion in activated CD8 T cells compared with CD86 costimulation.
485	17947667	We demonstrated increased CTLA-4 and programmed death-1 inhibitory molecule expression following costimulation by both CD80 and CD86 (CD80 > CD86).
486	17947667	Furthermore, T cells stimulated by CD80 were more susceptible to inhibition by CD4(+)CD25(+) T cells.
487	17947667	Overall, while CD86 does not stimulate an initial response as strongly as CD80, there is greater sustained activity that is seen even in the absence of continued costimulation.
488	17947667	CD86 has sustained costimulatory effects on CD8 T cells.
489	17947667	CD80 and CD86 both costimulate T cell activation.
490	17947667	We have studied mice expressing rat insulin promoter (RIP)-CD80 and RIP-CD86 on the NOD and NOD.scid genetic background to generate in vivo models, using diabetes as a readout for cytotoxic T cell activation.
491	17947667	However, the secondary in vivo response was maintained if T cells were activated through CD86 costimulation compared with CD80.
492	17947667	In vitro, CD80 costimulation enhanced cytotoxicity, proliferation, and cytokine secretion in activated CD8 T cells compared with CD86 costimulation.
493	17947667	We demonstrated increased CTLA-4 and programmed death-1 inhibitory molecule expression following costimulation by both CD80 and CD86 (CD80 > CD86).
494	17947667	Furthermore, T cells stimulated by CD80 were more susceptible to inhibition by CD4(+)CD25(+) T cells.
495	17947667	Overall, while CD86 does not stimulate an initial response as strongly as CD80, there is greater sustained activity that is seen even in the absence of continued costimulation.
496	17947667	CD86 has sustained costimulatory effects on CD8 T cells.
497	17947667	CD80 and CD86 both costimulate T cell activation.
498	17947667	We have studied mice expressing rat insulin promoter (RIP)-CD80 and RIP-CD86 on the NOD and NOD.scid genetic background to generate in vivo models, using diabetes as a readout for cytotoxic T cell activation.
499	17947667	However, the secondary in vivo response was maintained if T cells were activated through CD86 costimulation compared with CD80.
500	17947667	In vitro, CD80 costimulation enhanced cytotoxicity, proliferation, and cytokine secretion in activated CD8 T cells compared with CD86 costimulation.
501	17947667	We demonstrated increased CTLA-4 and programmed death-1 inhibitory molecule expression following costimulation by both CD80 and CD86 (CD80 > CD86).
502	17947667	Furthermore, T cells stimulated by CD80 were more susceptible to inhibition by CD4(+)CD25(+) T cells.
503	17947667	Overall, while CD86 does not stimulate an initial response as strongly as CD80, there is greater sustained activity that is seen even in the absence of continued costimulation.
504	17947667	CD86 has sustained costimulatory effects on CD8 T cells.
505	17947667	CD80 and CD86 both costimulate T cell activation.
506	17947667	We have studied mice expressing rat insulin promoter (RIP)-CD80 and RIP-CD86 on the NOD and NOD.scid genetic background to generate in vivo models, using diabetes as a readout for cytotoxic T cell activation.
507	17947667	However, the secondary in vivo response was maintained if T cells were activated through CD86 costimulation compared with CD80.
508	17947667	In vitro, CD80 costimulation enhanced cytotoxicity, proliferation, and cytokine secretion in activated CD8 T cells compared with CD86 costimulation.
509	17947667	We demonstrated increased CTLA-4 and programmed death-1 inhibitory molecule expression following costimulation by both CD80 and CD86 (CD80 > CD86).
510	17947667	Furthermore, T cells stimulated by CD80 were more susceptible to inhibition by CD4(+)CD25(+) T cells.
511	17947667	Overall, while CD86 does not stimulate an initial response as strongly as CD80, there is greater sustained activity that is seen even in the absence of continued costimulation.
512	17947667	CD86 has sustained costimulatory effects on CD8 T cells.
513	17947667	CD80 and CD86 both costimulate T cell activation.
514	17947667	We have studied mice expressing rat insulin promoter (RIP)-CD80 and RIP-CD86 on the NOD and NOD.scid genetic background to generate in vivo models, using diabetes as a readout for cytotoxic T cell activation.
515	17947667	However, the secondary in vivo response was maintained if T cells were activated through CD86 costimulation compared with CD80.
516	17947667	In vitro, CD80 costimulation enhanced cytotoxicity, proliferation, and cytokine secretion in activated CD8 T cells compared with CD86 costimulation.
517	17947667	We demonstrated increased CTLA-4 and programmed death-1 inhibitory molecule expression following costimulation by both CD80 and CD86 (CD80 > CD86).
518	17947667	Furthermore, T cells stimulated by CD80 were more susceptible to inhibition by CD4(+)CD25(+) T cells.
519	17947667	Overall, while CD86 does not stimulate an initial response as strongly as CD80, there is greater sustained activity that is seen even in the absence of continued costimulation.
520	17947667	CD86 has sustained costimulatory effects on CD8 T cells.
521	17947667	CD80 and CD86 both costimulate T cell activation.
522	17947667	We have studied mice expressing rat insulin promoter (RIP)-CD80 and RIP-CD86 on the NOD and NOD.scid genetic background to generate in vivo models, using diabetes as a readout for cytotoxic T cell activation.
523	17947667	However, the secondary in vivo response was maintained if T cells were activated through CD86 costimulation compared with CD80.
524	17947667	In vitro, CD80 costimulation enhanced cytotoxicity, proliferation, and cytokine secretion in activated CD8 T cells compared with CD86 costimulation.
525	17947667	We demonstrated increased CTLA-4 and programmed death-1 inhibitory molecule expression following costimulation by both CD80 and CD86 (CD80 > CD86).
526	17947667	Furthermore, T cells stimulated by CD80 were more susceptible to inhibition by CD4(+)CD25(+) T cells.
527	17947667	Overall, while CD86 does not stimulate an initial response as strongly as CD80, there is greater sustained activity that is seen even in the absence of continued costimulation.
528	18026823	We investigated the soluble costimulatory molecules CD80, CD86, CD28, and CTLA-4 and soluble adhesion molecules in plasma of 94 type 2 diabetic patients with or without nephropathy (DN and NDN) and 20 healthy controls.
529	18075857	Our data showed that the surface expressions of MHC II and CD86 on NOD-derived DC were increased after insulin treatment compared with those on PBS controlled mice.
530	18075857	The dendritic cells with a mature phenotype and increased MLR stimulation adoptively transferred immune tolerogenic effects in secondary NOD-SCID mice, which were associated with significant greater IL-10, TGF-beta production and CD4(+)CD25(+)T differentiation from splenocytes compared with NOD-SCID control recipients.
531	18453575	Preferential costimulation by CD80 results in IL-10-dependent TGF-beta1(+) -adaptive regulatory T cell generation.
532	18453575	Costimulatory ligands CD80 and CD86 have different binding preferences and affinities to their receptors, CD28 and CTLA-4.
533	18453575	Earlier, we demonstrated that CD80 binds to CTLA-4 with higher affinity and has a role in suppressing T cell response.
534	18453575	These T cells showed TGF-beta1 on their surface and secreted TGF-beta1 and IL-10 upon restimulation.
535	18453575	Although blockade of CTLA-4 and neutralization of IL-10 profoundly inhibited the induction of these TGF-beta1(+) T cells, their ability to suppress the effector T cell proliferation was abrogated by neutralization of TGF-beta1 alone.
536	18453575	Induction of TGF-beta1(+) and IL-10(+) T cells was found to be independent of natural CD4(+)CD25(+) regulatory T cells, demonstrating that preferential ligation of CTLA-4 by CD80 induced IL-10 production by effector T cells, which in turn promoted the secretion of TGF-beta1.
537	18453575	Treatment of prediabetic NOD mice with islet beta cell Ag-pulsed CD86(-/-) DCs, but not CD80(-/-) DCs, resulted in the induction of TGF-beta1- and IL-10-producing cells, significant suppression of insulitis, and delay of the onset of hyperglycemia.
538	18453575	These observations demonstrate not only that CD80 preferentially binds to CTLA-4 but also that interaction during Ag presentation can result in IL-10-dependent TGF-beta1(+) regulatory T cell induction, reinstating the potential of approaches to preferentially engage CTLA-4 through CD80 during self-Ag presentation in suppressing autoimmunity.
539	18453575	Preferential costimulation by CD80 results in IL-10-dependent TGF-beta1(+) -adaptive regulatory T cell generation.
540	18453575	Costimulatory ligands CD80 and CD86 have different binding preferences and affinities to their receptors, CD28 and CTLA-4.
541	18453575	Earlier, we demonstrated that CD80 binds to CTLA-4 with higher affinity and has a role in suppressing T cell response.
542	18453575	These T cells showed TGF-beta1 on their surface and secreted TGF-beta1 and IL-10 upon restimulation.
543	18453575	Although blockade of CTLA-4 and neutralization of IL-10 profoundly inhibited the induction of these TGF-beta1(+) T cells, their ability to suppress the effector T cell proliferation was abrogated by neutralization of TGF-beta1 alone.
544	18453575	Induction of TGF-beta1(+) and IL-10(+) T cells was found to be independent of natural CD4(+)CD25(+) regulatory T cells, demonstrating that preferential ligation of CTLA-4 by CD80 induced IL-10 production by effector T cells, which in turn promoted the secretion of TGF-beta1.
545	18453575	Treatment of prediabetic NOD mice with islet beta cell Ag-pulsed CD86(-/-) DCs, but not CD80(-/-) DCs, resulted in the induction of TGF-beta1- and IL-10-producing cells, significant suppression of insulitis, and delay of the onset of hyperglycemia.
546	18453575	These observations demonstrate not only that CD80 preferentially binds to CTLA-4 but also that interaction during Ag presentation can result in IL-10-dependent TGF-beta1(+) regulatory T cell induction, reinstating the potential of approaches to preferentially engage CTLA-4 through CD80 during self-Ag presentation in suppressing autoimmunity.
547	18850043	EEPHC significantly suppressed the expression of major histocompatibility complex (MHC) class II molecules and the costimulatory molecules CD40 and CD86 in NOD BM-DCs.
548	18850043	Furthermore, splenocytes from the protected mice produced high amounts of IL-4 and IL-10 and low levels of IL-2 and interferon gamma, suggesting that these DCs deficient in NF- kappaB activity are responsible for the apparent shift in type 2 helper T cells.
549	18941200	Freshly isolated human islet ECs constitutively expressed CD86 (B7-2) and ICOS ligand but not CD80 (B7-1) or CD40 costimulatory molecules.
550	18941200	The functional activity of islet EC-expressed CD86 was examined by coculture of resting islet ECs with CD4 T cells stimulated by CD3 ligation alone.
551	18941200	In keeping with this, adhesion/transmigration of activated (CD3 ligated) memory (CD45R0(+)) CD4 T cells across islet ECs was completely inhibited in the presence of CD86 blocking mAb.
552	18941200	Identical results were obtained for T cell adhesion using either CTLA-4 blocking mAb or CTLA-4Ig (abatacept), indicating CTLA-4 as the T cell ligand for these CD86-mediated effects.
553	18941200	These data suggest a novel role for CD86 expression on the microvasculature, whereby ligation of CTLA-4 on CD4 T cells by CD86 on islet ECs is key to the adhesion of recently activated T cells.
554	18941200	Freshly isolated human islet ECs constitutively expressed CD86 (B7-2) and ICOS ligand but not CD80 (B7-1) or CD40 costimulatory molecules.
555	18941200	The functional activity of islet EC-expressed CD86 was examined by coculture of resting islet ECs with CD4 T cells stimulated by CD3 ligation alone.
556	18941200	In keeping with this, adhesion/transmigration of activated (CD3 ligated) memory (CD45R0(+)) CD4 T cells across islet ECs was completely inhibited in the presence of CD86 blocking mAb.
557	18941200	Identical results were obtained for T cell adhesion using either CTLA-4 blocking mAb or CTLA-4Ig (abatacept), indicating CTLA-4 as the T cell ligand for these CD86-mediated effects.
558	18941200	These data suggest a novel role for CD86 expression on the microvasculature, whereby ligation of CTLA-4 on CD4 T cells by CD86 on islet ECs is key to the adhesion of recently activated T cells.
559	18941200	Freshly isolated human islet ECs constitutively expressed CD86 (B7-2) and ICOS ligand but not CD80 (B7-1) or CD40 costimulatory molecules.
560	18941200	The functional activity of islet EC-expressed CD86 was examined by coculture of resting islet ECs with CD4 T cells stimulated by CD3 ligation alone.
561	18941200	In keeping with this, adhesion/transmigration of activated (CD3 ligated) memory (CD45R0(+)) CD4 T cells across islet ECs was completely inhibited in the presence of CD86 blocking mAb.
562	18941200	Identical results were obtained for T cell adhesion using either CTLA-4 blocking mAb or CTLA-4Ig (abatacept), indicating CTLA-4 as the T cell ligand for these CD86-mediated effects.
563	18941200	These data suggest a novel role for CD86 expression on the microvasculature, whereby ligation of CTLA-4 on CD4 T cells by CD86 on islet ECs is key to the adhesion of recently activated T cells.
564	18941200	Freshly isolated human islet ECs constitutively expressed CD86 (B7-2) and ICOS ligand but not CD80 (B7-1) or CD40 costimulatory molecules.
565	18941200	The functional activity of islet EC-expressed CD86 was examined by coculture of resting islet ECs with CD4 T cells stimulated by CD3 ligation alone.
566	18941200	In keeping with this, adhesion/transmigration of activated (CD3 ligated) memory (CD45R0(+)) CD4 T cells across islet ECs was completely inhibited in the presence of CD86 blocking mAb.
567	18941200	Identical results were obtained for T cell adhesion using either CTLA-4 blocking mAb or CTLA-4Ig (abatacept), indicating CTLA-4 as the T cell ligand for these CD86-mediated effects.
568	18941200	These data suggest a novel role for CD86 expression on the microvasculature, whereby ligation of CTLA-4 on CD4 T cells by CD86 on islet ECs is key to the adhesion of recently activated T cells.
569	18941200	Freshly isolated human islet ECs constitutively expressed CD86 (B7-2) and ICOS ligand but not CD80 (B7-1) or CD40 costimulatory molecules.
570	18941200	The functional activity of islet EC-expressed CD86 was examined by coculture of resting islet ECs with CD4 T cells stimulated by CD3 ligation alone.
571	18941200	In keeping with this, adhesion/transmigration of activated (CD3 ligated) memory (CD45R0(+)) CD4 T cells across islet ECs was completely inhibited in the presence of CD86 blocking mAb.
572	18941200	Identical results were obtained for T cell adhesion using either CTLA-4 blocking mAb or CTLA-4Ig (abatacept), indicating CTLA-4 as the T cell ligand for these CD86-mediated effects.
573	18941200	These data suggest a novel role for CD86 expression on the microvasculature, whereby ligation of CTLA-4 on CD4 T cells by CD86 on islet ECs is key to the adhesion of recently activated T cells.
574	19050296	Elimination of the costimulatory molecule B7-2 prevents autoimmune diabetes in NOD mice, but leads to the development of a spontaneous autoimmune polyneuropathy (SAP), which resembles the human disease chronic inflammatory demyelinating polyneuropathy (CIDP).
575	19050296	In this study, we examined the immunopathogenic mechanisms in this model, including identification of SAP Ags.
576	19050296	There was an increase in IL-17 and a decrease in IL-10 transcript levels at 4 mo (preclinical phase), whereas IFN-gamma expression peaked at 8 mo (clinical phase).
577	19050296	There was also an increase in transcript levels of Th1 cytokines, CXCL10, and RANTES in sciatic nerves of mice that developed SAP.
578	19120268	Lowered expressions of the NF-kappaB family members in dendritic cells from NOD mice are associated with a reduced expression of GATA-2.
579	19120268	In the present study, we compared transcription profiles of CD11c(+) bone marrow (BM)-derived DCs from NOD mice with those from NON mice, focusing on the NF-kappaB/Rel family members and associated molecules.
580	19120268	The BMDCs from NOD mice displayed reduced mRNA expressions of NF-kappaB components, p65, p50, p52, and RelB, compared to NON mice: the proportions of each molecule relative to those of NON DCs were 53.9, 54.1, 54.0, and 37.0%, respectively, which were accompanied with lowered expressions of downstream immunomodulatory molecules, including IL-6, CD80, CD86, 4-1BB, and CD40.
581	19283894	In vitro, it inhibited the binding of both human and murine CD154 (CD40L) to their receptor (CD40) even in the presence of protein-containing media and prevented the CD154-induced proliferation of human B cells as well as the corresponding increase in surface expression of CD86, CD80, CD40, and MHC class II in a concentration-dependent manner.
582	19283894	Furthermore, in isolated human islets, it also decreased the CD154-induced release of inflammatory cytokines such as IFN-g, interleukin-6 (IL-6), and IL-8.
583	19283894	Suramin was selected for investigation because it has been reported to be an inhibitor of the interaction of TNF-a with its receptor and CD154 is a member of the TNF-family.
584	19380603	We investigated the effect of four distinct AGE subtypes (AGE-modified bovine serum albumin; AGE-2, AGE-3, AGE-4, and AGE-5) at concentrations ranging from 0.1 to 100 microg/ml on the expression of intercellular adhesion molecule-1, B7.1, B7.2, and CD40 on monocytes and its impact on the production of interferon-gamma and tumor necrosis factor-alpha in human peripheral blood mononuclear cells.
585	19497561	Costimulation via the PD-1 and B7-H1/B7-DC pathway regulates immunity.
586	19497561	A progressive increase in the expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the pancreatic lymph nodes of female non-obese diabetic (NOD) mice as they developed diabetes.
587	19497561	A significantly decreased expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the periphery of prediabetic NOD mice versus non-diabetic C57BL/6 strain.
588	19497561	In vivo blocking studies in NOD/B7-2KONOD mice revealed that B7-H1 and B7-DC positively costimulate autoreactive CD4 and CD8 T cells and may co-operate with B7-2 to augment priming and expansion of naïve autoreactive T cells.
589	19584865	Here we show that the CD2-specific fusion protein alefacept (lymphocyte function-associated antigen-3-Ig; LFA -3-Ig) selectively eliminates memory T cells and, when combined with a co-stimulation blockade-based regimen using cytotoxic T lymphocyte antigen-4 (CTLA-4)-Ig, a CD80- and CD86-specific fusion protein, prevents renal allograft rejection and alloantibody formation in nonhuman primates.
590	19700629	Because the engagement of intercellular adhesion molecule-1 (ICAM-1), B7.1, B7.2, and CD40 on monocytes with their ligands on T cells plays roles in cytokine production, we investigated the effects of AGE-2 and AGE-3 on the expressions of ICAM-1, B7.1, B7.2, and CD40 on monocytes, the production of interferon gamma and tumor necrosis factor alpha, and the lymphocyte proliferation in human peripheral blood mononuclear cells and their modulation by prostaglandin E(2) (PGE(2)).
591	19700629	The stimulation of EP(2) and EP(4) receptors is reported to increase cAMP levels.
592	19700629	The effects of PGE(2) were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by a dibutyryl cAMP and an adenylate cyclase activator, forskolin.
593	19914138	We investigated the effect of four distinct AGE subtypes (AGE-2/AGE-3/AGE-4/AGE-5) on the expressions of intracellular adhesion molecule (ICAM)-1, B7.1, B7.2 and CD40 on monocytes, the production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha and the proliferation of T-cells during human mixed lymphocyte reaction (MLR).
594	20030670	Those DCs that phagocytosed apoptotic cells diminished the expression of co-stimulatory molecules CD40 and CD86 and reduced secretion of proinflammatory cytokines.
595	20134434	Simultaneous detection of up to eight colors is enabled by careful selection and testing of cell-subset-defining monoclonal antibodies (anchor markers) in the appropriate fluorochrome combinations, in order to show the quantification of surface expression levels of molecules involved in chemotaxis (e.g., CX(3)CR1 and CCR2), adhesion (e.g., CD11b and CD62L), antigen presentation (e.g., CD83, CD86 and CD209) and immune regulation (e.g., CD101) on circulating APCs.
596	20558773	In previous work, we found that toxic AGEs, AGE-2 and AGE-3, induced the expression of intracellular adhesion molecule-1, B7.1, B7.2, and CD40 on monocytes, production of interferon-gamma and tumor necrosis factor alpha, and lymphocyte proliferation during human mixed lymphocyte reaction.
597	20558773	The effects of PGE2 were mimicked by an EP2 receptor agonist, ONO-AE1-259-01 (11,15-O-dimethyl PGE2), and an EP4 receptor agonist, ONO-AE1-329 [16-(3-methoxymethyl)phenyl-omega-tetranor-3,7dithia PGE1].
598	20558773	An EP2 receptor antagonist, AH6809 (6-isopropoxy-9-oxaxanthene-2-carboxylic acid), and an EP4 receptor antagonist, AH23848 [(4Z)-7-[(rel-1S,2S,5R)-5-((1,1'-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid], inhibited the actions of PGE2.
599	20558773	The stimulation of EP2 and EP4 receptors is reported to increase cAMP levels.
600	20558773	The effects of PGE2 were reversed by protein kinase A (PKA) inhibitors and mimicked by dibutyryl cAMP and an adenylate cyclase activator, forskolin.
601	20558773	These results as a whole indicate that PGE2 inhibited the actions of AGE-2 and AGE-3 via EP2/EP4 receptors and the cAMP/PKA pathway.
602	21678423	We found that F4/80(+) peritoneal exudate macrophages (PEMs) from mice with diabetes for 4 months displayed significantly reduced CD86 and CD54 expression and tumor necrosis factor (TNF)-α and IL-6 production but enhanced nitric oxide (NO) secretion compared with control mice when treated with interferon (IFN)-γ and lipopolysaccharide (LPS), while the activity of arginase in PEMs from diabetic mice was significantly higher than control mice when stimulating with IL-4.
603	21678423	In an in vitro culture system, high glucose and insulin significantly altered TNF-α, IL-6, and NO production and arginase activity of macrophages, which was reversed by the treatment with AKT and ERK inhibitors.
604	22002898	These precursors developed into CD11c(+) MHCII(+) CD86(+) DCs capable of processing DQ-OVA.
605	22156513	Here, we have reevaluated the contribution of CD28-CD80/86 costimulation in the LCMV system by use of CD80/86-deficient mice, and our results demonstrate that a disruption of CD28-CD80/86 signaling compromises the magnitude, phenotype, and/or functionality of LCMV-specific CD8(+) and/or CD4(+) T cell populations in all stages of the T cell response.
606	22156513	Notably, a profound inhibition of secondary T cell immunity in LCMV-immune CD80/86-deficient mice emerged as a composite of both defective memory T cell development and a specific requirement for CD80 but not CD86 in the recall response, while a related experimental scenario of CD28-dependent yet CD80/86-independent secondary CD8(+) T cell immunity suggests the existence of a CD28 ligand other than CD80/86.
607	22156513	Furthermore, we provide evidence that regulatory T cells (T(REG)s), the homeostasis of which is altered in CD80/86(-/-) mice, contribute to restrained LCMV-specific CD8(+) T cell responses in the presence of CD80/86.
608	22328150	Chemokine CCL2/MCP-1 is known to attract CCR2(+) monocytes and dendritic cells (DCs).
609	22328150	We have previously shown that transgenic expression of CCL2 in pancreatic islets via the rat insulin promoter induces nondestructive insulitis on a nonautoimmune background.
610	22328150	These DCs exhibited a hypoactive phenotype with low CD40, MHC II, CD80/CD86 expression, and reduced TNF-α but elevated IL-10 secretions.
611	22328150	These findings support an unexpected beneficial role for CCL2 in type 1 diabetes with implications for current strategies interfering with the CCL2/CCR2 axis in humans, and for dendritic cell biology in autoimmunity.
612	22579473	Interleukin-21 receptor-mediated signals control autoreactive T cell infiltration in pancreatic islets.
613	22579473	It remains unclear how interleukin-21 receptor (IL-21R) contributes to type 1 diabetes.
614	22579473	Here we have shown that dendritic cells (DCs) in the pancreas required IL-21R not for antigen uptake, but to acquire the chemokine receptor CCR7 and migrate into the draining lymph node.
615	22579473	Consequently, less antigen, major histocompatibility complex (MHC) class II, and CD86 was provided to autoreactive effector cells in Il21r(-/-) mice, impairing CD4(+) T cell activation, CD40:CD40L interactions, and pancreatic infiltration by autoreactive T cells.
616	22579473	CD40 crosslinking restored defective CD4(+) cell expansion and CD4 independently expanded autoreactive CD8(+) cells, but CD8(+) cells still required CD4(+) cells to reach the pancreas and induce diabetes.
617	22579473	We conclude that IL-21R controls both antigen transport by DCs and the crucial beacon function of CD4(+) cells for autoreactive CD8(+) cells to reach the islets.
618	22698916	Autoantigen upregulates CD86 in anti-insulin B cells, suggesting they are competent to interact with T cells.
619	23055693	Belatacept belongs to a new class of immunosuppressive drugs that selectively inhibits T-cell activation by preventing CD28 activation and by binding its ligands B7-1 and B7-2.
620	23293354	The critical role of CTLA-4 in inhibiting Ag-driven T cell responses upon engagement with its ligands, B7-1 and B7-2 and its importance for peripheral T cell tolerance and T cell homeostasis has been studied intensively.
621	23638101	Contrary, EV1 infection, which resulted in lower virus input at the same MOI, resulted in DC activation as observed by production of type I interferon-stimulated genes (ISGs), upregulation of co-stimulatory and co-inhibitory molecules (CD80, CD86, PDL1) and production of IL-6 and TNF-α, with a relative moderate decrease in cell viability.
622	23710834	Beyond the impact on survival in M2, RAPA reduced CXCR4, CD206 and CD209 expression and stem cell growth factor-β, CCL18 and CCL13 release.
623	23710834	In contrast, in M1 RAPA increased CD86 and CCR7 expression and IL-6, tumour necrosis factor-α and IL-1β release but reduced CD206 and CD209 expression and IL-10, vascular endothelial growth factor and CCL18 release.
624	23715623	In vitro exposure of bone marrow-derived DCs to TGF-β reduced expression of costimulatory molecules CD80 and CD86, as well as production of proinflammatory cytokines such as interleukin-12 p70 in DCs, but did not alter levels of major histocompatibility complex classes I and II.
625	23715623	Furthermore, the capacity of TGF-β-treated bone marrow-derived DCs to activate both CD4(+) and CD8(+) T cells was reduced.
626	23804272	We have discovered a method to induce stable tolerogenic ability to dendritic cells ex vivo using a mixture of phosphorothioate-modified antisense DNA targeting the primary transcripts of CD40, CD80 and CD86.
627	23911738	CD80, CD86, CD28, CTLA4, ICOS and CD25 mRNA expression was characterized in 49 newly diagnosed young T1D patients (mean age 11 ± 5 years, 25 male/24 women) and 31 controls (mean age 14 ± 7 years, 14 male/17 women).
628	23911738	In addition, polymorphisms in CTLA4 (rs231806, rs231775, rs3087243) were genotyped and soluble CTLA4 plasma levels measured by ELISA.
629	23911738	T1D patients presented with higher peripheral blood expression levels of CD80 (Mann-Whitney U-test, p=0.0001) and lower ICOS levels compared to healthy controls (Glm adjusted for age, p=0.0004).
630	23911738	CD80 expression in T1D patients correlated with expression of two CTLA4 splice variants (Spearman's rank correlation, rho=0.56, p=0.0002 for sCTLA4; rho=0.61, p<0.0001 for flCTLA4).
631	23911738	In controls, CD80 expression correlated with CD25 expression (Spearman's rank correlation, rho=0.57, p=0.002).
632	23911738	We also found a tendency that the CTLA4 +49A/G polymorphism influenced sCTLA4 mRNA expression in T1D individuals and was lowest in individuals with the GG genotype (Mann-Whitney U-test, p=0.039).
633	23911738	To summarize, we expect that newly diagnosed T1D among children and adolescents is associated with activation of CD80 and CTLA4 in peripheral blood.
634	23911738	Additional studies will be needed to elucidate the role of CD80/CTLA4 signaling in T1D.
635	23993652	Here we have shown that eTACs are a discrete major histocompatibility complex class II (MHC II)(hi), CD80(lo), CD86(lo), epithelial cell adhesion molecule (EpCAM)(hi), CD45(lo) bone marrow-derived peripheral antigen-presenting cell (APC) population.