Ohnishi H, Tanaka T, Takahara J, Kotb M
Veteran's Affairs Medical Center, Memphis, TN 38104.
J Immunol. 1993 Apr 15;150(8 Pt 1):3207-14.
The CD28 pathway functions to provide costimulatory signals that are required for TCR-mediated activation of T cells. The role of this pathway in superantigenic stimulation of resting human T cells was investigated in the presence and absence of APC using a streptococcal superantigen, pep M5. Anti-B7/BB1 mAb inhibited the response of T cells when pep M5 was presented by APC. In the absence of APC, cross-linking CD28 by anti-CD28 mAb provides signals that synergize with APC-derived cytokines and with superantigen resulting in T cell proliferation. Anti-HLA-DR, -DQ mAb blocked the response of T cells to pep M5 presented by APC but had no effect on the response of purified T cells to the superantigen costimulated via CD28 cross-linking. These data show that the CD28 pathway is important for superantigenic stimulation of T cells and that signaling through this pathway can substitute for the APC-associated costimulatory activity that is essential for T cell stimulation. Moreover, the results are consistent with the notion that, in the presence of appropriate costimulation, pep M5 can directly interact with T cells and induce them to proliferate.
CD28 信号通路的功能是提供共刺激信号，这是 TCR 介导的 T 细胞活化所必需的。使用链球菌超抗原 pep M5，在有和没有抗原呈递细胞（APC）的情况下，研究了该信号通路在静息人 T 细胞超抗原刺激中的作用。当 pep M5 由 APC 呈递时，抗 B7/BB1 单克隆抗体抑制 T 细胞的反应。在没有 APC 的情况下，抗 CD28 单克隆抗体交联 CD28 可提供与 APC 衍生的细胞因子以及超抗原协同作用的信号，从而导致 T 细胞增殖。抗 HLA-DR、-DQ 单克隆抗体阻断了 T 细胞对 APC 呈递的 pep M5 的反应，但对纯化的 T 细胞对通过 CD28 交联共刺激的超抗原的反应没有影响。这些数据表明，CD28 信号通路对于 T 细胞的超抗原刺激很重要，并且通过该信号通路的信号传导可以替代对 T 细胞刺激至关重要的与 APC 相关的共刺激活性。此外，结果与以下观点一致：在存在适当共刺激的情况下，pep M5 可以直接与 T 细胞相互作用并诱导它们增殖。
