ICOS mediates the development of insulin-dependent diabetes mellitus in nonobese diabetic mice.
Initiation of diabetes in NOD mice can be mediated by the costimulatory signals received by T cells. The ICOS is found on Ag-experienced T cells where it acts as a potent regulator of T cell responses. To determine the function of ICOS in diabetes, we followed the course of autoimmune disease and examined T cells in ICOS-deficient NOD mice. The presence of ICOS was indispensable for the development of insulitis and hyperglycemia in NOD mice. In T cells, the deletion of ICOS resulted in a decreased production of the Th1 cytokine IFN-gamma, whereas the numbers of regulatory T cells remained unchanged. We conclude that ICOS is critically important for the induction of the autoimmune process that leads to diabetes.
Hawiger
Daniel
D
Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Tran
Elise
E
Du
Wei
W
Booth
Carmen J
CJ
Wen
Li
L
Dong
Chen
C
Flavell
Richard A
RA
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000502:physiology*; D001323:Autoantibodies / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma