IL-21 limits NK cell responses and promotes antigen-specific T cell activation: A mediator of the transition from innate to adaptive immunity
IL-21 limits NK cell responses and promotes antigen-specific T cell activation: A mediator of the transition from innate to adaptive immunity
复制标题
DOI：
10.1016/s1074-7613(02)00295-9
复制
发表时间：
2002-04-01
期刊：
影响因子：
32.4
通讯作者：
Grusby, MJ
中科院分区：
文献类型：
--
作者：
Kasaian, MT;Whitters, MJ;Grusby, MJ
干扰素α/β、IL-12和IL-15调节NK细胞的激活和扩增，但在诱导获得性免疫时触发NK反应的信号仍未确定。我们现在报道，IL-21，一种激活的T细胞的产物，可能具有这一功能。缺乏IL-21R(IL-21R-/-)的小鼠有正常的NK细胞发育，但没有检测到对IL-21的反应。IL-21增强了激活的小鼠NK细胞的细胞毒活性和干扰素-γ的产生，但不支持其活性，从而限制了其激活的持续时间。此外，IL-21阻断了IL-15诱导的静息NK细胞的扩张，从而阻止了进一步的先天反应的启动。相反，IL-21促进了同种异体MLR中CD8(+)效应T细胞的增殖、IFN-γ的产生和细胞毒功能。这些观察表明，IL-21促进了先天免疫和获得性免疫之间的转换。
IFNalpha/beta, IL-12, and IL-15 regulate NK cell activation and expansion, but signals triggering resolution of the NK response upon induction of adaptive immunity remain to be defined. We now report that IL-21, a product of activated T cells, may serve this function. Mice lacking IL-21 R (IL-21 R-/-) had normal NK cell development but no detectable responses to IL-21. IL-21 enhanced cytotoxic activity and IFNgamma production by activated murine NK cells but did not support their viability, thus limiting their duration of activation. Furthermore, IL-21 blocked IL-15-induced expansion of resting NK cells, thus preventing the initiation of further innate responses. In contrast, IL-21 enhanced the proliferation, IFNgamma production, and cytotoxic function of CD8(+) effector T cells in an allogeneic MLR. These observations suggest that IL-21 promotes the transition between innate and adaptive immunity.