Bishop D K, Li W
Department of Medicine, University of Utah School of Medicine, Salt Lake City 84132.
J Immunol. 1992 Feb 15;148(4):1049-54.
Modified limiting dilution analysis techniques were used to evaluate the effects of the immunosuppressants cyclosporin A (CsA) and FK506 on alloantigen-induced T cell activation in vivo. Treatment of sponge matrix allograft recipients with either CsA or FK506 inhibited lymphocytic infiltration of the allograft, a process thought to be dependent on local lymphokine production. In addition, both immunosuppressants markedly reduced the absolute number of lymphocytes recovered from the draining lymph nodes (LN) and prevented CTL activation in the LN. However, Ag-primed helper T lymphocytes (HTL) were present in the draining LN of sponge allograft recipients treated with CsA, but not in recipients treated with FK506. T cell depletion experiments were performed to determine the phenotype of primed HTL in the LN of untreated and CsA-treated sponge allograft recipients. In untreated sponge allograft recipients, CD4+ and CD8+ Ag-primed HTL were present in the draining LN in equivalent numbers. In contrast, the majority of primed HTL in the LN of CsA-treated sponge allograft recipients were CD8+, rather than CD4+ T cells. These observations indicate that CsA and FK506 exert distinct in vivo effects at the level of HTL priming, and CD4+ and CD8+ HTL exhibit differential sensitivity to CsA in vivo.
采用改良的有限稀释分析技术，评估免疫抑制剂环孢素A（CsA）和FK506对体内同种异体抗原诱导的T细胞活化的影响。用CsA或FK506治疗海绵基质同种异体移植受体，可抑制同种异体移植的淋巴细胞浸润，这一过程被认为依赖于局部淋巴因子的产生。此外，两种免疫抑制剂均显著降低了从引流淋巴结（LN）中回收的淋巴细胞绝对数量，并阻止了LN中的CTL活化。然而，在用CsA治疗的海绵同种异体移植受体的引流LN中存在抗原致敏的辅助性T淋巴细胞（HTL），而在用FK506治疗的受体中则不存在。进行T细胞耗竭实验，以确定未治疗和经CsA治疗的海绵同种异体移植受体的LN中致敏HTL的表型。在未治疗的海绵同种异体移植受体中，引流LN中存在数量相当的CD4+和CD8+抗原致敏HTL。相比之下，经CsA治疗的海绵同种异体移植受体的LN中，大多数致敏HTL是CD8+，而非CD4+ T细胞。这些观察结果表明，CsA和FK506在HTL致敏水平上发挥不同的体内作用，并且CD4+和CD8+ HTL在体内对CsA表现出不同的敏感性。
