title: NK cells regulate CD4 responses prior to antigen encounter.
abstract: NK cells not only respond rapidly to infection, shaping subsequent adaptive immunity, but also play a role in regulating autoimmune disease. The ability of NK cells to influence adaptive immunity before Ag exposure was examined in a gender-dependent model of preferential Th1 and Th2 activation. The inability of young adult male SJL mice to activate Th1 cells was reversed via depletion of NK1.1(+) cells, whereas the presence or the absence of NK1.1(+) cells did not alter responses in age-matched females. Consistent with a gender-dependent role in regulating adaptive immunity, significantly more NK1.1(+) cells were present in males compared with females, and this difference was reversed by castration. In contrast to NK1.1(+) cells derived from C57BL/6 mice, no spontaneous cytokine secretion was detected in NK1.1(+) cells derived from either male or female SJL mice, although an increased frequency of IL-10-secreting NK1.1(+) cells was observed in males vs females following in vitro stimulation. Direct evidence that NK1.1(+) cells in males influence CD4(+) T cell activation before Ag exposure was demonstrated via the adoptive transfer of APC from control and NK1.1-depleted males. The absence of a functional NK T cell population in SJL mice suggests that NK cells influence adaptive immunity before Ag exposure via alterations in APC activity.
authors.affiliation: Department of Neurology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Kennichi C
authors.initials: KC
authors.lastname: Dowdell
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cua
authors.forename: Erlinda
authors.initials: E
authors.lastname: Kirkman
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stohlman
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D000941:Antigens / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012727:Sex Characteristics; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000941:Antigens; D016753:Interleukin-10; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin