Kerstan Andreas, Hünig Thomas
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
J Immunol. 2004 Feb 1;172(3):1341-5. doi: 10.4049/jimmunol.172.3.1341.
TCR-driven clonal expansion of T cells is limited by activation-induced cell death through CD95/CD95L interactions. This cell-contact dependent mechanism is attenuated by costimulation through CD28. Here, we show that primary rat lymph node T cells activated by "superagonistic" CD28-specific mAb, which do not require TCR-engagement for full T cell activation, do not up-regulate CD95L. CD28 superagonist activated T cells are highly resistant to artificial CD95 cross-linking, and display a marked up-regulation of the survival factor Bcl-x(L). Consistently, NF-kappaB factors, known to promote Bcl-x(L) transcription, are strongly activated by superagonistic CD28 mAb stimulation. In contrast, a weaker induction of NFAT, which positively regulates the CD95L gene, in CD28 activated cells as compared with TCR- or TCR/CD28-stimulated cells was observed. Thus, by recruiting the mitogenic activity of CD28 in the absence of TCR engagement, the anti-apoptotic signals provided by costimulation are revealed without interfering proapoptotic effects induced by TCR stimulation.
通过CD95/CD95L相互作用的活化诱导细胞死亡限制了T细胞受体驱动的T细胞克隆扩增。这种细胞接触依赖性机制通过CD28共刺激而减弱。在此，我们表明，由“超激动性”CD28特异性单克隆抗体激活的原代大鼠淋巴结T细胞，其完全激活不需要T细胞受体参与，不会上调CD95L。CD28超激动剂激活的T细胞对人工CD95交联具有高度抗性，并显示存活因子Bcl-x(L)显著上调。一致地，已知促进Bcl-x(L)转录的核因子κB因子被超激动性CD28单克隆抗体刺激强烈激活。相比之下，与T细胞受体或T细胞受体/CD28刺激的细胞相比，在CD28激活的细胞中观察到正向调节CD95L基因的活化T细胞核因子（NFAT）诱导较弱。因此，通过在没有T细胞受体参与的情况下募集CD28的促有丝分裂活性，揭示了共刺激提供的抗凋亡信号，而不干扰T细胞受体刺激诱导的促凋亡效应。
