Nisbet-Brown E R, Lee J W, Cheung R K, Gelfand E W
J Immunol. 1987 Jun 1;138(11):3713-9.
We have directly compared the signals required for: induction of the [Ca+2]i response, expression of Tac antigen, and proliferation in antigen-specific human T cell clones. We have previously shown that antigen-specific activation of cloned T cells under conditions leading to proliferation is accompanied by a rapid increase in [Ca+2]i. Cloned T cells showed increased [Ca+2]i, enhanced Tac expression, and proliferated in response to specific antigen in the presence of viable, genetically appropriate antigen-presenting cells. Paraformaldehyde fixation of antigen-presenting cells after "pulsing" with antigen prevented proliferation, but did not affect MHC-restricted [Ca+2]i or Tac responses. Treatment of cloned T cells with monoclonal anti-T3 antibody also increased [Ca+2]i and Tac expression but did not induce proliferation. Proliferation was restored by viable autologous or allogenic APC or exogenous IL 2, but not by IL 1. In contrast to resting T cells, T cell clones were insensitive to the mitogenic effects of lectins or of ionophores and phorbol esters. These results suggest that activation of antigen-specific T cells requires the sequential action of at least two signals. The first is MHC restricted and is mediated by interaction of antigen + MHC class II products with the T cell receptor (T3-Ti) complex. This leads to Tac expression and increased [Ca+2]i, but is not sufficient for proliferation. This signal can be bypassed by anti-T3 monoclonal antibodies. Proliferation requires a second, nonantigen-specific, non-MHC-restricted antigen-presenting cell signal, which cannot be replaced by IL 1 in our system. This signal can be bypassed, however, by the addition of exogenous IL 2 to cells that have received the first signal and express Tac, suggesting that it is required for IL 2 synthesis and secretion. T cell clones therefore provide a useful model for studying antigen-dependent and -independent events in cell activation.
我们直接比较了诱导[Ca+2]i反应、Tac抗原表达以及抗原特异性人T细胞克隆增殖所需的信号。我们之前已经表明，在导致增殖的条件下，克隆T细胞的抗原特异性激活伴随着[Ca+2]i的快速增加。克隆T细胞在有活力的、基因匹配的抗原呈递细胞存在的情况下，对特异性抗原反应时[Ca+2]i增加、Tac表达增强并发生增殖。用抗原“脉冲”后，对抗原呈递细胞进行多聚甲醛固定可阻止增殖，但不影响MHC限制的[Ca+2]i或Tac反应。用单克隆抗T3抗体处理克隆T细胞也会增加[Ca+2]i和Tac表达，但不会诱导增殖。有活力的自体或同种异体抗原呈递细胞或外源性IL-2可恢复增殖，但IL-1不能。与静息T细胞不同，T细胞克隆对凝集素、离子载体和佛波酯的促有丝分裂作用不敏感。这些结果表明，抗原特异性T细胞的激活至少需要两个信号的顺序作用。第一个信号受MHC限制，由抗原+MHC II类产物与T细胞受体（T3-Ti）复合物的相互作用介导。这导致Tac表达和[Ca+2]i增加，但不足以促进增殖。该信号可被抗T3单克隆抗体绕过。增殖需要第二个非抗原特异性、非MHC限制的抗原呈递细胞信号，在我们的系统中该信号不能被IL-1替代。然而，对于已接收第一个信号并表达Tac的细胞，添加外源性IL-2可绕过该信号，这表明它是IL-2合成和分泌所必需的。因此，T细胞克隆为研究细胞激活中抗原依赖性和非依赖性事件提供了一个有用的模型。
