Cutting edge: a novel mechanism bridging innate and adaptive immunity: IL-12 induction of CD25 to form high-affinity IL-2 receptors on NK cells.
NK cell expression and use of the IL-2Rα-chain (CD25), required for the high-affinity IL-2R, remain poorly understood. The studies reported in this article demonstrate that infections with murine CMV (MCMV), but not with lymphocytic choriomeningitis virus, induce CD25 on NK cells, along with high levels of IL-12 and IL-18. The cytokines act ex vivo to increase CD25 levels, and IL-12, IL-12R, and STAT4, but not the NK activating receptor Ly49H, are required for peak induction in vivo. All examined NK cell populations are driven into proliferation and incorporate BrdU in response to high ex vivo concentrations of IL-2, but only those from MCMV infection respond to low ex vivo concentrations of IL-2. The numbers of NK cells elicited during MCMV infection are reduced by IL-2 neutralization. Thus, a link between innate and adaptive immunity is established by which composition of innate cytokine responses sets up to promote NK cell use of a factor supporting adaptive responses.
Department of Molecular Microbiology and Immunology, Division of Biology and Medicine and Warren Alpert Medical School, Brown University, Providence, RI 02912, USA.
Seung-Hwan
SH
Lee
Maria F
MF
Fragoso
Christine A
CA
Biron
D056704:Adaptive Immunity; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000502:physiology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism
C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D015375:Receptors, Interleukin-2; D018664:Interleukin-12