Kondrack Robyn M, Harbertson Judith, Tan Joyce T, McBreen Meghan E, Surh Charles D, Bradley Linda M
Department of Immunology, The Sidney Kimmel Cancer Center, 10835 Altman Row, San Diego, CA 92121, USA.
J Exp Med. 2003 Dec 15;198(12):1797-806. doi: 10.1084/jem.20030735. Epub 2003 Dec 8.
Cytokines, particularly those of the common gamma chain receptor family, provide extrinsic signals that regulate naive CD4 cell survival. Whether these cytokines are required for the maintenance of memory CD4 cells has not been rigorously assessed. In this paper, we examined the contribution of interleukin (IL) 7, a constitutively produced common gamma chain receptor cytokine, to the survival of resting T cell receptor transgenic memory CD4 cells that were generated in vivo. IL-7 mediated the survival and up-regulation of Bcl-2 by resting memory CD4 cells in vitro in the absence of proliferation. Memory CD4 cells persisted for extended periods upon adoptive transfer into intact or lymphopenic recipients, but not in IL-7- mice or in recipients that were rendered deficient in IL-7 by antibody blocking. Both central (CD62L+) and effector (CD62L-) memory phenotype CD4 cells required IL-7 for survival and, in vivo, memory cells were comparable to naive CD4 cells in this regard. Although the generation of primary effector cells from naive CD4 cells and their dissemination to nonlymphoid tissues were not affected by IL-7 deficiency, memory cells failed to subsequently develop in either the lymphoid or nonlymphoid compartments. The results demonstrate that IL-7 can have previously unrecognized roles in the maintenance of memory in the CD4 cell population and in the survival of CD4 cells with a capacity to become memory cells.
细胞因子，尤其是那些常见γ链受体家族的细胞因子，可提供调节初始CD4细胞存活的外在信号。这些细胞因子对于记忆性CD4细胞的维持是否必需，尚未得到严格评估。在本文中，我们研究了白细胞介素（IL）-7（一种组成性产生的常见γ链受体细胞因子）对体内产生的静止T细胞受体转基因记忆性CD4细胞存活的作用。在无增殖的情况下，IL-7在体外介导静止记忆性CD4细胞的存活及Bcl-2的上调。记忆性CD4细胞在过继转移至完整或淋巴细胞减少的受体后能长期存活，但在IL-7基因敲除小鼠或通过抗体阻断使IL-7缺乏的受体中则不能。中枢（CD62L +）和效应（CD62L -）记忆表型的CD4细胞的存活均需要IL-7，并且在这方面，体内记忆细胞与初始CD4细胞相当。尽管初始CD4细胞产生初始效应细胞并将其扩散至非淋巴组织不受IL-7缺乏的影响，但记忆细胞随后在淋巴或非淋巴区室中均无法发育。结果表明，IL-7在CD4细胞群体记忆的维持以及具有成为记忆细胞能力的CD4细胞的存活中可能具有先前未被认识的作用。
