TGF-BETA-1 ALTERS APC PREFERENCE, POLARIZING ISLET ANTIGEN RESPONSES TOWARD A TH2 PHENOTYPE

TGF-beta 1, expressed in the pancreatic islets, protects the nonobese diabetic (NOD) mouse from insulin-dependent diabetes mellitus (IDDM). The islet antigen-specific T cell response of ins-TGF-beta 1 mice reli ed on different antigen-presenting cells (APC) from those used by NOD T cells. T cells from NOD mice utilized B cells to present islet antig en, whereas T cells from ins-TGF-beta 1 mice utilized macrophages. In addition, the islet antigen-specific T cell repertoire of ins-TGF-beta 1 mice was distinct and deviated toward an IL-4-producing Th2 phenoty pe. When ins-TGF-beta 1 mice were treated with anti-IL-4 antibody, isl et antigen-specific IFN gamma-producing Th1 cells were unleashed, and the incidence of diabetes increased to the level of NOD mice. This sug gests active suppression of a diabetogenic T cell response. This study describes a novel mechanism in which expression of TGF-beta 1 in the context of self-antigen shifts APC preference, deviating T cell respon ses to a Th2 phenotype, preventing IDDM.