CD28-B7 interactions allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help.
CD28-B7 interactions allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help.
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DOI：
10.1084/jem.177.6.1791
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发表时间：
1993-06-01
影响因子：
15.3
通讯作者：
Allison, J P
中科院分区：
文献类型：
--
作者：
Harding, F A;Allison, J P
对于产生CD 8+细胞毒性T细胞（CTL）的活化要求知之甚少。在这里，我们证明了在没有外源性帮助的情况下，CD 28-B7相互作用对于产生I类主要组织相容性复合体特异性CTL是必要的和足够的。共刺激仅在反应的诱导期需要，而在效应期不需要。将CD 28反受体B7转染到非刺激性P815细胞中赋予了引发P815特异性CTL的能力，并且这种应答可以被抗CD 28 Fab或嵌合B7结合蛋白CTLA 4 Ig抑制。抗CD 28单克隆抗体（mAb）可在脾刺激因子的共刺激能力被化学固定破坏时向CD 8 + T细胞提供共刺激信号。CD 28介导的信号传导引起白细胞介素2（IL-2）从CD 8 + CTL前体的释放，因为抗CD 28 mAb可以通过添加IL-2来替代，并且抗IL-2 mAb可以阻断抗CD 28诱导的CTL的产生。CD 4+细胞不参与所检查系统中的共刺激反应。我们得出结论，CD 8 + T细胞活化需要两个信号：由T细胞受体介导的抗原特异性信号，以及通过CD 28-B7相互作用提供的额外抗原非特异性信号。
The activation requirements for the generation of CD8+ cytotoxic T cells (CTL) are poorly understood. Here we demonstrate that in the absence of exogenous help, a CD28-B7 interaction is necessary and sufficient for generation of class I major histocompatibility complex- specific CTL. Costimulation is required only during the inductive phase of the response, and not during the effector phase. Transfection of the CD28 counter receptor, B7, into nonstimulatory P815 cells confers the ability to elicit P815-specific CTL, and this response can be inhibited by anti-CD28 Fab or by the chimeric B7-binding protein CTLA4Ig. Anti- CD28 monoclonal antibody (mAb) can provide a costimulatory signal to CD8+ T cells when the costimulatory capacity of splenic stimulators is destroyed by chemical fixation. CD28-mediated signaling provokes the release of interleukin 2 (IL-2) from the CD8+ CTL precursors, as anti- CD28 mAb could be substituted for by the addition of IL-2, and an anti- IL-2 mAb can block the generation of anti-CD28-induced CTL. CD4+ cells are not involved in the costimulatory response in the systems examined. We conclude that CD8+ T cell activation requires two signals: an antigen-specific signal mediated by the T cell receptor, and an additional antigen nonspecific signal provided via a CD28-B7 interaction.