NK cells regulate CD4 responses prior to antigen encounter |
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Authors: | Dowdell Kennichi C Cua Daniel J Kirkman Erlinda Stohlman Stephen A |
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Institution: | Department of Neurology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA. |
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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. |
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