King C, Davies J, Mueller R, Lee M S, Krahl T, Yeung B, O'Connor E, Sarvetnick N
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Immunity. 1998 May;8(5):601-13. doi: 10.1016/s1074-7613(00)80565-8.
TGF-beta1, 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-beta1 mice relied on different antigen-presenting cells (APC) from those used by NOD T cells. T cells from NOD mice utilized B cells to present islet antigen, whereas T cells from ins-TGF-beta1 mice utilized macrophages. In addition, the islet antigen-specific T cell repertoire of ins-TGF-beta1 mice was distinct and deviated toward an IL-4-producing Th2 phenotype. When ins-TGF-beta1 mice were treated with anti-iL-4 antibody, islet antigen-specific IFNGamma-producing Th1 cells were unleashed, and the incidence of diabetes increased to the level of NOD mice. This suggests active suppression of a diabetogenic T cell response. This study describes a novel mechanism in which expression of TGF-beta1 in the context of self-antigen shifts APC preference, deviating T cell responses to a Th2 phenotype, preventing IDDM.
在胰岛中表达的转化生长因子β1（TGF-β1）可保护非肥胖糖尿病（NOD）小鼠免受胰岛素依赖型糖尿病（IDDM）的侵害。胰岛特异性TGF-β1小鼠的胰岛抗原特异性T细胞反应所依赖的抗原呈递细胞（APC）与NOD T细胞所使用的不同。NOD小鼠的T细胞利用B细胞呈递胰岛抗原，而胰岛特异性TGF-β1小鼠的T细胞利用巨噬细胞。此外，胰岛特异性TGF-β1小鼠的胰岛抗原特异性T细胞库是独特的，并偏向于产生白细胞介素-4（IL-4）的辅助性T细胞2（Th2）表型。当用抗IL-4抗体治疗胰岛特异性TGF-β1小鼠时，产生干扰素γ（IFNγ）的胰岛抗原特异性辅助性T细胞1（Th1）细胞被释放出来，糖尿病发病率增加到NOD小鼠的水平。这表明对致糖尿病T细胞反应有主动抑制作用。本研究描述了一种新机制，即TGF-β1在自身抗原背景下的表达改变了APC偏好，使T细胞反应偏向Th2表型，从而预防IDDM。
