Cytokine-induced survival of activated T cells in vitro and in vivo
Cytokine-induced survival of activated T cells in vitro and in vivo
复制标题
DOI：
10.1073/pnas.95.7.3810
复制
发表时间：
1998-03-31
影响因子：
11.1
通讯作者：
Marrack, P
中科院分区：
文献类型：
--
作者：
Vella, AT;Dow, S;Marrack, P
在动物中，许多抗原特异性T细胞在暴露于抗原后死亡。如果在活化后不久从动物中分离并培养这些细胞，则它们也会死亡。测试了各种细胞因子干扰这种体外死亡的能力。令人惊讶的是，肿瘤坏死因子α和其他炎性细胞因子没有阻止活化T细胞的体外死亡，即使这些细胞因子确实阻止了动物中的活化T细胞死亡。四种细胞因子，白细胞介素（IL）-2，IL-3，IL-7和IL-15，在体外确实阻止活化的T细胞死亡，其中IL-4和IL-15比IL-2或IL-7更有效。这些细胞因子共享它们的受体的一个组成部分，共同的γ链，γ c。因此，它们保护活化的T细胞免于死亡的集体能力可能由涉及γ c的信号介导。为了评估它们的体内活性，在动物中在超抗原应答的局部位点表达两种细胞因子IL-2和IL-4。两种细胞因子均增加了14天后在局部部位发现的T细胞数量。白细胞介素4比IL-2更有效，即使IL-2比IL-1更好地刺激T细胞增殖。这一结果表明，IL-4和相关细胞因子可以促进T细胞在体内和体外的存活。这些细胞因子防止活化T细胞死亡的能力在动物免疫应答的某些阶段可能是重要的。
Many antigen-specific T cells die after exposure to antigen in animals. These cells also die if they are isolated from animals shortly after activation and cultured, Various cytokines were tested for their ability to interfere with this in vitro death, Surprisingly, tumor necrosis factor a and other inflammatory cytokines did not prevent the in vitro death of activated T cells, even though these cytokines do prevent activated T cell death in animals, Therefore, the inflammatory cytokines probably act on T cells in vivo via an intermediary factor, Four cytokines, interleukin (IL)-2, IL-3, IL-7, and IL-15, did prevent activated T cell death in vitro, with IL-4 and IL-15 more effective than IL-2 or IL-7. These cytokines share a component of their receptors, the common gamma chain, gamma c. Therefore, their collective ability to protect activated T cells from death mag be mediated by signals involving gamma c, To assess their activity in vivo, two of the cytokines, IL-2 and IL-4, were expressed in animals at local sites of superantigen responses. Both cytokines increased the numbers of T cells found al the local sites 14 days later. Interleukin 4 was more effective than IL-2, even though IL-2 stimulates T cell proliferation better than IL-il. This result suggested that IL-4 and related cytokines can promote T cell survival in vivo as well as in vitro. The ability of these cytokines to prevent the death of activated T cells mar be important at certain stages of immune responses in animals.