Kimura H, Davies T F
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
Clin Immunol Immunopathol. 1991 Feb;58(2):195-206. doi: 10.1016/0090-1229(91)90136-x.
Strains of rat differ in their susceptibility to experimental autoimmune thyroiditis (EAT). We recently observed that the normal Wistar rat has lymph node (LN) T cells which recognize the newly available cloned Wistar thyroid cell line (WRT) and/or rat thyroglobulin (rTg). We have now cloned thyroid-specific T cells and characterized their interaction with the WRT target cell. Twenty-three T cell clones were tested for their reactivity to syngeneic thymocytes, WRT cells alone, or WRT cells with thymocytes. All the clones were of the CD4+CD8- phenotype. Seven of 23 T cell clones proliferated in the presence of WRT cells alone or with the combination of WRT cells and thymocytes, exhibiting stimulation indices of 1.5 to 5. In all but one of the T cell clones responding to WRT cells alone was there no evidence that the additional presence of thymocytes supplied a stronger "second" proliferative signal than the WRT cells. These WRT-reactive clones which were able to be more extensively characterized were MHC class II restricted, secreted rat interferon (IFN)-gamma in response to WRT cell exposure, and one clone showed cross-reactivity with rTg antigen. Induction of WRT cell MHC class II antigen by prior treatment with IFN-gamma failed to further enhance the WRT cell-induced T cell proliferation. These data provide the first evidence for direct antigen presentation by thyroid epithelial cells (TECs) in the absence of other antigen-presenting cells. Furthermore, they provide evidence that TECs are able to provide the appropriate "second" signals required for T cell activation and successful autoantigen presentation.
大鼠品系对实验性自身免疫性甲状腺炎(EAT)的易感性存在差异。我们最近观察到,正常的Wistar大鼠具有能够识别新获得的克隆Wistar甲状腺细胞系(WRT)和/或大鼠甲状腺球蛋白(rTg)的淋巴结(LN)T细胞。我们现已克隆出甲状腺特异性T细胞,并对其与WRT靶细胞的相互作用进行了表征。检测了23个T细胞克隆对同基因胸腺细胞、单独的WRT细胞或WRT细胞与胸腺细胞组合的反应性。所有克隆均为CD4 + CD8 - 表型。23个T细胞克隆中有7个在单独存在WRT细胞或WRT细胞与胸腺细胞组合的情况下增殖,刺激指数为1.5至5。在所有对单独的WRT细胞有反应的T细胞克隆中,除了一个之外,没有证据表明胸腺细胞的额外存在提供了比WRT细胞更强的“第二”增殖信号。这些能够更广泛表征的对WRT有反应的克隆受MHC II类限制,在暴露于WRT细胞时分泌大鼠干扰素(IFN)-γ,并且一个克隆与rTg抗原表现出交叉反应性。用IFN-γ预先处理诱导WRT细胞MHC II类抗原未能进一步增强WRT细胞诱导的T细胞增殖。这些数据首次证明了在没有其他抗原呈递细胞的情况下甲状腺上皮细胞(TEC)可直接呈递抗原。此外,它们提供了证据表明TEC能够提供T细胞活化和成功自身抗原呈递所需的适当“第二”信号。