B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes.
CD28/B7 costimulation has been implicated in the induction and progression of autoimmune diseases. Experimentally induced models of autoimmunity have been shown to be prevented or reduced in intensity in mice rendered deficient for CD28 costimulation. In sharp contrast, spontaneous diabetes is exacerbated in both B7-1/B7-2-deficient and CD28-deficient NOD mice. These mice present a profound decrease of the immunoregulatory CD4+CD25+ T cells, which control diabetes in prediabetic NOD mice. These cells are absent from both CD28KO and B7-1/B7-2KO mice, and the transfer of this regulatory T cell subset from control NOD animals into CD28-deficient animals can delay/prevent diabetes. The results suggest that the CD28/ B7 costimulatory pathway is essential for the development and homeostasis of regulatory T cells that control spontaneous autoimmune diseases.
Salomon
B
B
Committee on Immunology, Ben May Institute for Cancer Research and Department of Pathology, University of Chicago, Illinois 60637, USA.
Lenschow
D J
DJ
Rhee
L
L
Ashourian
N
N
Singh
B
B
Sharpe
A
A
Bluestone
J A
JA
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D006706:Homeostasis; D018796:Immunoconjugates; D008213:Lymphocyte Activation / Q000276:immunology*; D008222:Lymphokines / Q000172:deficiency; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D011236:Prediabetic State / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D008222:Lymphokines; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D000069594:Abatacept