Sperling A I, Auger J A, Ehst B D, Rulifson I C, Thompson C B, Bluestone J A
Ben May Institute, University of Chicago, IL 60637, USA.
J Immunol. 1996 Nov 1;157(9):3909-17.
CD28/B7 ligation provides costimulatory signals important for the development of T cell responses. In the present study, we examined whether CD28/B7 interactions have a specialized role in the regulation of cell cycle progression and sustained T cell proliferative responses in naive T cell populations using TCR transgenic mice. CD28-mediated signaling was shown to be uniquely capable of regulating cell survival compared with TCR-mediated signaling. Increasing the strength of the TCR-mediated signal 1 increased early proliferative responses, but had no effect on sustained cell survival. In contrast, CD28 ligation, signal 2, was not required for early proliferative responses, but dramatically influenced long term T cell survival. The increased cell survival after CD28 ligation was not due to increased IL-2 production, but was linked to up-regulation of Bcl-xL. The Bcl-xL protein could not be induced following increased TCR cross-linking in the absence of CD28 signaling. In addition, survival of T cells from Bcl-xL transgenic mice was not inhibited by blocking CD28 ligation, suggesting that CD28-induced T cell survival is regulated by Bcl-xL expression. Together, these results suggest that the unique role of CD28 signaling is not to costimulate the initial activation of naive T cells, but is, in fact, to sustain the late proliferative response and enhance long term cell survival.
CD28/B7连接提供对T细胞反应发展至关重要的共刺激信号。在本研究中，我们使用TCR转基因小鼠，研究了CD28/B7相互作用在调节幼稚T细胞群体的细胞周期进程和持续T细胞增殖反应中是否具有特殊作用。与TCR介导的信号相比，CD28介导的信号被证明具有独特的调节细胞存活的能力。增强TCR介导的信号1的强度可增加早期增殖反应，但对持续的细胞存活没有影响。相反，早期增殖反应不需要CD28连接（信号2），但它对T细胞的长期存活有显著影响。CD28连接后细胞存活增加并非由于IL-2产生增加，而是与Bcl-xL的上调有关。在没有CD28信号的情况下，TCR交联增加后无法诱导Bcl-xL蛋白。此外，阻断CD28连接不会抑制来自Bcl-xL转基因小鼠的T细胞存活，这表明CD28诱导的T细胞存活受Bcl-xL表达调节。总之，这些结果表明，CD28信号的独特作用不是共刺激幼稚T细胞的初始激活，而是实际上维持晚期增殖反应并增强长期细胞存活。
