Manickasingham S P, Anderton S M, Burkhart C, Wraith D C
Department of Pathology and Microbiology, University of Bristol School of Medical Sciences, United Kingdom.
J Immunol. 1998 Oct 15;161(8):3827-35.
The CD28/B7 system provides costimulatory signals necessary for optimal T cell activation. We have examined the effects of blocking B7.1 and/or B7.2 in an in vitro system using TCR transgenic T cells specific for myelin basic protein. Activation of naive T cells was found to be B7.2 dependent and not dependent on the presence of B7.1 molecules. However, increasing the strength of signal through the TCR using peptide analogues with higher affinity for MHC compensated for blockade of B7.2 molecules, suggesting that signal 1 alone can be sufficient for the activation of naive T cells. The role of B7 molecules in the differentiation of T cells was further investigated by restimulating T cells with fresh APC and peptide in B7-sufficient conditions. A down-regulation of IL-2 and IFN-gamma production by T cells primed in the presence of anti-B7.2 mAb was partially overcome when high affinity peptide analogues were used to restimulate T cells. In contrast, a significant down-regulation of the differentiation of cells producing Th-2 cytokines was observed in the presence of anti-B7 Abs. Differentiation of IL-4-secreting cells was influenced by both B7.1 and B7.2, while IL-5 secretion was totally dependent on B7.2. These results suggest that B7-mediated costimulation is essential for the development of Th-2-associated cytokines, the absence of which cannot be overcome by increasing the strength of the signal through the TCR.
CD28/B7系统提供了最佳T细胞激活所需的共刺激信号。我们使用针对髓鞘碱性蛋白的TCR转基因T细胞，在体外系统中研究了阻断B7.1和/或B7.2的效果。发现初始T细胞的激活依赖于B7.2，而不依赖于B7.1分子的存在。然而，使用对MHC具有更高亲和力的肽类似物来增强通过TCR的信号强度，可补偿对B7.2分子的阻断，这表明仅信号1就足以激活初始T细胞。通过在B7充足的条件下用新鲜的抗原呈递细胞和肽再次刺激T细胞，进一步研究了B7分子在T细胞分化中的作用。当使用高亲和力肽类似物再次刺激T细胞时，在抗B7.2单克隆抗体存在下启动的T细胞产生的IL-2和IFN-γ的下调得到了部分克服。相反，在抗B7抗体存在下，观察到产生Th-2细胞因子的细胞分化显著下调。分泌IL-4的细胞的分化受B7.1和B7.2两者影响，而IL-5的分泌则完全依赖于B7.2。这些结果表明，B7介导的共刺激对于Th-2相关细胞因子的发育至关重要，增加通过TCR的信号强度无法克服其缺失。
