Jaleco Sara, Swainson Louise, Dardalhon Valérie, Burjanadze Maryam, Kinet Sandrina, Taylor Naomi
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5535/Institut Fédératif de Recherche 122, Montpellier, France.
J Immunol. 2003 Jul 1;171(1):61-8. doi: 10.4049/jimmunol.171.1.61.
Cytokines play a crucial role in the maintenance of polyclonal naive and memory T cell populations. It has previously been shown that ex vivo, the IL-7 cytokine induces the proliferation of naive recent thymic emigrants (RTE) isolated from umbilical cord blood but not mature adult-derived naive and memory human CD4(+) T cells. We find that the combination of IL-2 and IL-7 strongly promotes the proliferation of RTE, whereas adult CD4(+) T cells remain relatively unresponsive. Immunological activity is controlled by a balance between proliferation and apoptotic cell death. However, the relative contributions of IL-2 and IL-7 in regulating these processes in the absence of MHC/peptide signals are not known. Following exposure to either IL-2 or IL-7 alone, RTE, as well as mature naive and memory CD4(+) T cells, are rendered only minimally sensitive to Fas-mediated cell death. However, in the presence of the two cytokines, Fas engagement results in a high level of caspase-dependent apoptosis in both RTE as well as naive adult CD4(+) T cells. In contrast, equivalently treated memory CD4(+) T cells are significantly less sensitive to Fas-induced cell death. The increased susceptibility of RTE and naive CD4(+) T cells to Fas-induced apoptosis correlates with a significantly higher IL-2/IL-7-induced Fas expression on these T cell subsets than on memory CD4(+) T cells. Thus, IL-2 and IL-7 regulate homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in RTE and mature naive and memory T cell subsets.
细胞因子在维持多克隆幼稚和记忆性T细胞群体中发挥着关键作用。此前已有研究表明，在体外，白细胞介素-7（IL-7）细胞因子可诱导从脐带血中分离出的幼稚近期胸腺迁出细胞（RTE）增殖，但不能诱导成熟的成人来源幼稚和记忆性人类CD4(+) T细胞增殖。我们发现，IL-2和IL-7的组合强烈促进RTE的增殖，而成年CD4(+) T细胞仍然相对无反应。免疫活性由增殖和凋亡性细胞死亡之间的平衡控制。然而，在缺乏主要组织相容性复合体/肽信号的情况下，IL-2和IL-7在调节这些过程中的相对作用尚不清楚。单独暴露于IL-2或IL-7后，RTE以及成熟的幼稚和记忆性CD4(+) T细胞对Fas介导的细胞死亡仅表现出最低程度的敏感性。然而，在两种细胞因子存在的情况下，Fas激活导致RTE以及幼稚成人CD4(+) T细胞中高水平的半胱天冬酶依赖性凋亡。相比之下，同等处理的记忆性CD4(+) T细胞对Fas诱导的细胞死亡明显不敏感。RTE和幼稚CD4(+) T细胞对Fas诱导凋亡的易感性增加与这些T细胞亚群上IL-2/IL-7诱导的Fas表达显著高于记忆性CD4(+) T细胞相关。因此，IL-2和IL-7通过调节RTE以及成熟幼稚和记忆性T细胞亚群中增殖和凋亡性细胞死亡之间的平衡来调节体内平衡。
