Van Parijs L, Peterson D A, Abbas A K
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Immunity. 1998 Feb;8(2):265-74. doi: 10.1016/s1074-7613(00)80478-1.
We have examined the role of Fas and Bcl-2 in T cell survival and responses to antigen in vivo using T cells that express a transgenic antigen receptor specific for hen egg lysozyme (HEL) and that either lack functional Fas or Fas ligand (FasL) or overexpress Bcl-2 as a transgene. HEL-specific, Bcl-2-transgenic T cells showed prolonged responses to immunization with cognate peptide but were eliminated rapidly when exposed to HEL expressed systemically as a self antigen. In contrast, Fas- and FasL-defective T cells did not display exaggerated responses to immunization with HEL peptide, but did show increased expansion and survival in response to systemic self antigen and were able to activate anti-HEL (self) antibody-forming cells. Thus, Bcl-2 and Fas play different roles in the regulation of T cell responses to antigen in vivo and in self tolerance.
我们利用表达对鸡卵溶菌酶（HEL）具有特异性的转基因抗原受体的T细胞，研究了Fas和Bcl-2在体内T细胞存活及对抗原反应中的作用，这些T细胞要么缺乏功能性Fas或Fas配体（FasL），要么作为转基因过度表达Bcl-2。对同源肽免疫反应时，表达HEL特异性且转基因Bcl-2的T细胞显示出延长的反应，但当作为自身抗原全身性暴露于HEL时会迅速被清除。相比之下，Fas和FasL缺陷的T细胞对HEL肽免疫反应时未表现出过度反应，但对全身性自身抗原反应时确实显示出增加的扩增和存活，并且能够激活抗HEL（自身）抗体形成细胞。因此，Bcl-2和Fas在体内T细胞对抗原反应的调节以及自身耐受性方面发挥着不同作用。
