IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity.
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.
Pubmed ID: 11970879 RIS Download
Animals | Antigens, CD44 | Apoptosis | CD8-Positive T-Lymphocytes | Cytotoxicity, Immunologic | Female | Immunity, Active | Immunity, Innate | Interleukin-15 | Interleukin-21 Receptor alpha Subunit | Interleukins | Isoantigens | Killer Cells, Natural | Lymphocyte Activation | Lymphocyte Count | Male | Mice | Mice, Inbred BALB C | Mice, Inbred C57BL | Mice, Knockout | Receptors, Interleukin | Receptors, Interleukin-2 | Receptors, Interleukin-21