title: IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity.
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.
authors.affiliation: Genetics Institute, Wyeth Research, Cambridge, MA 02140, USA.
authors.forename: Marion T
authors.initials: MT
authors.lastname: Kasaian
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Whitters
authors.forename: Laura L
authors.initials: LL
authors.lastname: Carter
authors.forename: Leslie D
authors.initials: LD
authors.lastname: Lowe
authors.forename: Jason M
authors.initials: JM
authors.lastname: Jussif
authors.forename: Bijia
authors.initials: B
authors.lastname: Deng
authors.forename: Kaley A
authors.initials: KA
authors.lastname: Johnson
authors.forename: JoAnn S
authors.initials: JS
authors.lastname: Witek
authors.forename: Mayra
authors.initials: M
authors.lastname: Senices
authors.forename: Richard F
authors.initials: RF
authors.lastname: Konz
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Wurster
authors.forename: Debra D
authors.initials: DD
authors.lastname: Donaldson
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Young
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Grusby
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology; D007110:Immunity, Active; D007113:Immunity, Innate; D019409:Interleukin-15 / Q000276:immunology; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21
chemical_list: D018960:Hyaluronan Receptors; C508118:Il21r protein, mouse; D019409:Interleukin-15; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D007519:Isoantigens; D018123:Receptors, Interleukin; D015375:Receptors, Interleukin-2; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21