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., and Grusby, Michael J.
IFNα/β, 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 IFNγ 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, IFNγ 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. [Copyright &y& Elsevier]