Abstract
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. 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. 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. These results support the suggestion that CD80 and CD86 mainly differ at the level of the intensity of the signals they deliver.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD / biosynthesis*
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Antigens, CD / genetics
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Autoimmunity / genetics*
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B7-1 Antigen / biosynthesis*
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B7-2 Antigen
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Cell Movement / immunology
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Crosses, Genetic
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Diabetes Mellitus, Experimental / genetics*
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Diabetes Mellitus, Experimental / immunology*
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Diabetes Mellitus, Experimental / pathology
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Disease Progression
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Histocompatibility Antigens Class II / genetics
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Insulin / genetics
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Islets of Langerhans / immunology*
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Islets of Langerhans / metabolism
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Islets of Langerhans / pathology
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Lymphocyte Activation / genetics
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Transgenic
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Promoter Regions, Genetic / immunology
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Rats
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T-Lymphocytes / immunology
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T-Lymphocytes / pathology
Substances
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Antigens, CD
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B7-1 Antigen
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B7-2 Antigen
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Cd86 protein, mouse
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Cd86 protein, rat
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Histocompatibility Antigens Class II
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Insulin
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Membrane Glycoproteins