Kasaian Marion T, Whitters Matthew J, Carter Laura L, Lowe Leslie D, Jussif Jason M, Deng Bijia, Johnson Kaley A, Witek JoAnn S, Senices Mayra, Konz Richard F, Wurster Andrea L, Donaldson Debra D, Collins Mary, Young Deborah A, Grusby Michael J
Genetics Institute, Wyeth Research, Cambridge, MA 02140, USA.
Immunity. 2002 Apr;16(4):559-69. doi: 10.1016/s1074-7613(02)00295-9.
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-21R (IL-21R(-/-)) 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.
干扰素α/β、白细胞介素-12和白细胞介素-15调节自然杀伤细胞（NK细胞）的激活和扩增，但在适应性免疫诱导时触发NK细胞反应消退的信号仍有待确定。我们现在报告，活化T细胞的产物白细胞介素-21可能发挥这一功能。缺乏白细胞介素-21受体（IL-21R(-/-)）的小鼠NK细胞发育正常，但对白细胞介素-21无明显反应。白细胞介素-21增强了活化的小鼠NK细胞的细胞毒性活性和γ干扰素产生，但不支持其存活，因此限制了它们的激活持续时间。此外，白细胞介素-21阻断白细胞介素-15诱导的静息NK细胞扩增，从而阻止进一步先天反应的启动。相反，在同种异体混合淋巴细胞反应中，白细胞介素-21增强了CD8(+)效应T细胞的增殖、γ干扰素产生和细胞毒性功能。这些观察结果表明，白细胞介素-21促进先天免疫和适应性免疫之间的转变。
