IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity |
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Authors: | 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 |
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Institution: | Genetics Institute, Wyeth Research, Cambridge, MA 02140, USA. |
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Abstract: | 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. |
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