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.
Kasaian
Marion T
MT
Genetics Institute, Wyeth Research, Cambridge, MA 02140, USA.
Whitters
Matthew J
MJ
Carter
Laura L
LL
Lowe
Leslie D
LD
Jussif
Jason M
JM
Deng
Bijia
B
Johnson
Kaley A
KA
Witek
JoAnn S
JS
Senices
Mayra
M
Konz
Richard F
RF
Wurster
Andrea L
AL
Donaldson
Debra D
DD
Collins
Mary
M
Young
Deborah A
DA
Grusby
Michael J
MJ
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
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