Durum S K, Gershon R K
Proc Natl Acad Sci U S A. 1982 Aug;79(15):4747-50. doi: 10.1073/pnas.79.15.4747.
Antigen-primed T cells have been shown to require I-region-compatible adherent cells, as well as the priming antigen, to proliferate in vitro. We postulated that the Ia-recognition event is required for the T cell to induce secretion of the monokine interleukin 1 (IL 1) from adherent cells; the conventionally held view is that Ia is directly required for T cell activation. Our hypothesis predicts that IL I could replace the requirement for Ia+ cells in T cell proliferation assays in vitro. To test this prediction, we depleted keyhole limpet hemocyanin (KLH)-primed C57BL/6 mouse lymph node cells of I-A+ cells by treating with monoclonal anti-I-Ab and complement. As expected, this treatment eliminated the ability of KLH to provoke a proliferative response by primed T cells. Proliferation was restored by providing exogenous IL 1, but only in conjunction with added KLH. The proliferative response of primed T cells could also be blocked by adding anti-I-Ab to culture, and this inhibition could similarly be reversed by providing IL 1 in the presence of the specific antigen KLH. On the basis of these findings we propose a model of T cell activation and discuss its implications.
抗原致敏的T细胞已被证明在体外增殖时需要I区相容的黏附细胞以及致敏抗原。我们推测,T细胞诱导黏附细胞分泌单核因子白细胞介素1(IL-1)需要Ia识别事件;传统观点认为,T细胞激活直接需要Ia。我们的假设预测,在体外T细胞增殖试验中,IL-1可以取代对Ia⁺细胞的需求。为了验证这一预测,我们用单克隆抗I-Ab和补体处理了血蓝蛋白(KLH)致敏的C57BL/6小鼠淋巴结细胞,以去除其中的I-A⁺细胞。正如预期的那样,这种处理消除了KLH激发致敏T细胞增殖反应的能力。通过提供外源性IL-1可恢复增殖,但前提是同时添加KLH。向培养物中添加抗I-Ab也可阻断致敏T细胞的增殖反应,在存在特异性抗原KLH的情况下提供IL-1同样可逆转这种抑制作用。基于这些发现,我们提出了一个T细胞激活模型并讨论了其意义。