Zeng Rong, Spolski Rosanne, Finkelstein Steven E, Oh SangKon, Kovanen Panu E, Hinrichs Christian S, Pise-Masison Cynthia A, Radonovich Michael F, Brady John N, Restifo Nicholas P, Berzofsky Jay A, Leonard Warren J
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
J Exp Med. 2005 Jan 3;201(1):139-48. doi: 10.1084/jem.20041057.
Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor gamma chain (gamma(c)), which is mutated in humans with X-linked severe combined immunodeficiency. We now report that IL-21 synergistically acts with IL-15 to potently promote the proliferation of both memory (CD44high) and naive (CD44low) phenotype CD8+ T cells and augment interferon-gamma production in vitro. IL-21 also cooperated, albeit more weakly, with IL-7, but not with IL-2. Correspondingly, the expansion and cytotoxicity of CD8+ T cells were impaired in IL-21R-/- mice. Moreover, in vivo administration of IL-21 in combination with IL-15 boosted antigen-specific CD8+ T cell numbers and resulted in a cooperative effect on tumor regression, with apparent cures of large, established B16 melanomas. Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15.
白细胞介素（IL）-21是最近发现的一类共享细胞因子受体γ链（γ(c)）的细胞因子，在患有X连锁重症联合免疫缺陷的人类中，该链发生了突变。我们现在报告，IL-21与IL-15协同作用，有力地促进记忆型（CD44高）和初始型（CD44低）表型的CD8+ T细胞增殖，并在体外增强干扰素-γ的产生。IL-21也与IL-7协同作用，尽管协同作用较弱，但不与IL-2协同。相应地，IL-21R基因敲除小鼠中CD8+ T细胞的扩增和细胞毒性受损。此外，在体内联合给予IL-21和IL-15可增加抗原特异性CD8+ T细胞数量，并对肿瘤消退产生协同作用，明显治愈了已形成的大型B16黑色素瘤。因此，我们的研究表明，IL-21主要在与IL-15协同的情况下，有力地调节CD8+ T细胞的扩增和效应功能。
Zotero 插件
