McLeod J D, Walker L S, Patel Y I, Boulougouris G, Sansom D M
Bath Institute for Rheumatic Diseases, Department of Pharmacy and Pharmacology, University of Bath, United Kingdom.
J Immunol. 1998 Mar 1;160(5):2072-9.
Ag recognition is an essential component for an effective T cell response. However, T cell activation is also subject to additional regulation by accessory molecules. CD28 provides essential costimulatory signals that allow T cells to proliferate, whereas molecules such as CTLA-4 and CD95 (Fas) appear to be negative regulators. Currently, which outcome predominates under conditions of antigenic challenge is poorly understood. In particular it has been suggested that one consequence of antigenic activation of T cells is the up-regulation of both CD95 and CD95 ligand, thereby exposing activated T cells to apoptotic death. We have investigated this possibility in normal human peripheral blood T cells triggered by the superantigen SEB either in the presence of endogenous APCs or transfectants expressing DR4 and CD80. In either case, we find that such activation does not expose the majority of T cells to anti-CD95-induced apoptosis as detected by annexin V externalization and DNA fragmentation. Furthermore, by phenotypically identifying, by flow cytometry, those cells that received both antigenic and costimulatory signals from those cells that did not, we observed that CD95-induced apoptosis was not seen in activated T cells receiving Ag and costimulatory signals via CD28. However, while not all T cells were stimulated by superantigen, CD95 expression was found to be homogeneously up-regulated, suggesting a mechanism whereby bystander cells might be made susceptible to CD95-induced death. We conclude that antigenic activation of T cells via the TCR and CD28 engagement provides protection from CD95-induced apoptosis.
抗原识别是有效的T细胞应答的一个重要组成部分。然而，T细胞活化也受到辅助分子的额外调控。CD28提供必要的共刺激信号，使T细胞得以增殖，而诸如CTLA-4和CD95（Fas）等分子似乎是负调节因子。目前，在抗原刺激条件下哪种结果占主导地位还知之甚少。特别值得一提的是，有人提出T细胞抗原活化的一个后果是CD95及其配体的上调，从而使活化的T细胞面临凋亡死亡。我们在内源性抗原呈递细胞（APC）存在的情况下，或在表达DR4和CD80的转染细胞中，研究了超抗原SEB触发的正常人外周血T细胞中这种可能性。在这两种情况下，我们发现，通过膜联蛋白V外化和DNA片段化检测，这种活化并未使大多数T细胞暴露于抗CD95诱导的凋亡。此外，通过流式细胞术从表型上区分那些接收到抗原和共刺激信号的细胞与未接收到这些信号的细胞，我们观察到，通过CD28接收到抗原和共刺激信号的活化T细胞中未出现CD95诱导的凋亡。然而，虽然并非所有T细胞都受到超抗原刺激，但发现CD95表达均一性上调，这提示了一种机制，通过该机制旁观者细胞可能会变得易于发生CD95诱导的死亡。我们得出结论，T细胞通过TCR和CD28结合的抗原活化可提供针对CD95诱导凋亡的保护作用。
