Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin 2.
Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin 2.
复制标题
白介素 2 调节免疫干扰素和细胞毒性 T 淋巴细胞的产生。
作者：
W. Farrar;H. Johnson;J. Farrar
同种异体抗原特异性细胞毒性T淋巴细胞前体的活化依赖于巨噬细胞和辅助T细胞或来自这些促进细胞的调节分子的存在。已经鉴定了三种生物化学上不同的辅助因子：白细胞介素1（巨噬细胞衍生的）、白细胞介素2（T细胞衍生的）和免疫干扰素。所有3种因子均存在于混合淋巴细胞培养物（MLC）的上清液中，然而，从这些培养物中去除巨噬细胞完全消除了这些因子的产生以及细胞毒性T淋巴细胞（CTL）的诱导。向这些巨噬细胞耗尽的MLC中添加IL 2恢复了应答T细胞的能力：1）绕过对巨噬细胞可溶性功能的需求，2）产生免疫干扰素，以及3）产生CTL。免疫干扰素产生的动力学和剂量反应与IL 2的产生相关。免疫干扰素的产生以及CTL的产生需要T细胞、同种异体抗原和IL 2。此外，IL 2诱导的CTL被加入抗免疫干扰素所中和。这些数据表明：1）免疫干扰素产生的调节是基于由IL 2介导的T细胞与T细胞的相互作用，和2）免疫干扰素产生可能是IL 2诱导CTL所必需的。这些发现与以下假设一致：CTL的诱导涉及线性细胞因子相互作用，其中IL 1（巨噬细胞衍生的）刺激T细胞产生IL 2，IL 2又刺激其他T细胞产生免疫干扰素并变得具有细胞毒性。
The activation of alloantigen-specific cytotoxic T lymphocyte precursors is dependent upon the presence of both macrophages and helper T cells or regulatory molecules derived from these facilitative cells. Three biochemically distinct helper factors have been identified: interleukin 1 (macrophage-derived), Interleukin 2 (T cell derived), and immune interferon. All 3 factors are found in supernatants of mixed lymphocyte cultures (MLC), however, the removal of macrophages from these cultures completely ablates the production of these factors as well as the induction of cytotoxic T lymphocytes (CTL). The addition of IL 2 to these macrophage-depleted MLC restores the ability of responder T cells to: 1) bypass the requirement for macrophage soluble function, 2) produce immune interferon, and 3) generate CTL. The kinetics and dose response of immune interferon production in response to IL 2 correlates with the generation of CTL. The production of immune interferon as well as the generation of CTL requires T cells, alloantigen, and IL2. Furthermore, the induction of CTL by IL2 was neutralized by the addition of anti-immune interferon. These data suggest that: 1) the regulation of immune interferon production is based on a T to T cell interaction mediated by IL 2, and 2) immune interferon production may be required for IL 2 induction of CTL. These findings are consistent with the hypothesis that the induction of CTL involves a linear cell-factor interaction in which IL 1 (macrophage-derived) stimulates T cells to produce IL 2, which in turn stimulates other T cells to produce immune interferon and become cytotoxic.