Regulatory T cells can mediate their function through the stimulation of APCs to produce immunosuppressive nitric oxide.
Regulatory T cells (Tr cells) play a critical role in inducing immune tolerance. It remains largely unclear how various types of Tr cells perform their regulatory function. We have studied the underlying regulatory mechanism of a population of autoantigen-specific CD4+ Tr cells. These T cells are specific for the glutamic acid decarboxylase p206-220 peptide and are isolated from the diabetes-resistant nonobese-resistant mice. Although these T cells express T-bet and display a Th1 phenotype, they are able to inhibit diabetes. Their regulatory function is dependent on both IFN-gamma and cell contact with target cells. These Tr cells can mediate their cell contact-dependent regulatory function by secreting IFN-gamma which stimulates APCs to produce NO. NO is necessary for the Tr cells to inhibit the proliferation of pathogenic T cells and the development of diabetes. Therefore, we have identified a novel mechanism by which these Tr cells can exert their regulatory function. These results also provide an explanation as to why IFN-gamma may play both pathogenic and immunomodulatory roles in autoimmune diseases.
Chen
Cyndi
C
Division of Immunology, Beckman Research Institute, City of Hope, 1450 East Duarte Road, Duarte, CA 91010-3000, USA.
Lee
Wen-hui
WH
Zhong
Lingwen
L
Liu
Chih-Pin
CP
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D002450:Cell Communication; D002469:Cell Separation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology
D009569:Nitric Oxide; D007371:Interferon-gamma