Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function.

Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function.
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DOI:
10.1084/jem.20041057
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发表时间:
2005-01-03
影响因子:
15.3
通讯作者:
Leonard, WJ
Leonard, WJ
中科院分区:
医学1区
文献类型:
--
作者:
Zeng, R;Spolski, R;Finkelstein, SE;Oh, SK;Kovanen, PE;Hinrichs, CS;Pise-Masison, CA;Radonovich, MF;Brady, JN;Restifo, NP;Berzofsky, JA;Leonard, WJ

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白细胞介素 (IL)-21 是最近被认可的细胞因子,它们具有共同的细胞因子受体 γ 链 (γc),该细胞因子在患有 X 连锁严重联合免疫缺陷的人类中发生突变。我们现在报道,IL-21 与 IL-15 协同作用,有效促进记忆 (CD44high) 和幼稚 (CD44low) 表型 CD8+ T 细胞的增殖,并增加体外干扰素 γ 的产生。 IL-21 也与 IL-7 合作,尽管较弱,但与 IL-2 不合作。相应地,IL-21R−/− 小鼠中 CD8+ T 细胞的扩增和细胞毒性受到损害。此外,体内给予IL-21与IL-15组合可增加抗原特异性CD8+T细胞数量,并对肿瘤消退产生协同作用,明显治愈大型B16黑色素瘤。因此,我们的研究表明,IL-21 有效调节 CD8+ T 细胞扩增和效应器功能,主要是在与 IL-15 协同的情况下。
Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor γ chain (γc), 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-γ 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.
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