Autoimmunity without diabetes in transgenic mice expressing beta cell-specific CD86, but not CD80: parameters that trigger progression to diabetes.
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.
Guerder
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S
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Eynon
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EE
Flavell
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RA
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D002465:Cell Movement / Q000276:immunology; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000276:immunology; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; C497966:Cd86 protein, rat; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D008562:Membrane Glycoproteins