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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / immunology
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CD8-Positive T-Lymphocytes / immunology*
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Cytotoxicity, Immunologic
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Female
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Hyaluronan Receptors / immunology
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Immunity, Active
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Immunity, Innate
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Interleukin-15 / immunology
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Interleukin-21 Receptor alpha Subunit
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Interleukins / immunology*
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Interleukins / pharmacology
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Isoantigens / immunology
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Killer Cells, Natural / cytology
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Killer Cells, Natural / immunology*
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Lymphocyte Activation / immunology*
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Lymphocyte Count
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Interleukin / genetics
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Receptors, Interleukin / immunology
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Receptors, Interleukin-2 / biosynthesis
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Receptors, Interleukin-21
Substances
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Hyaluronan Receptors
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Il21r protein, mouse
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Interleukin-15
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Interleukin-21 Receptor alpha Subunit
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Interleukins
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Isoantigens
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Receptors, Interleukin
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Receptors, Interleukin-2
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Receptors, Interleukin-21
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interleukin-21