Gender-dependent IL-12 secretion by APC is regulated by IL-10.
Female SJL mice preferentially mount Th1-immune responses and are susceptible to the active induction of experimental allergic encephalomyelitis. By contrast, young adult male SJL are resistant to experimental allergic encephalomyelitis due to an APC-dependent induction of Th2 cells. The basis for this gender-dependent differential T cell induction was examined by analysis of macrophage APC cytokine secretion during T cell activation. APC derived from females secrete IL-12, but not IL-10, during T cell activation. By contrast, APC derived from males secrete IL-10, but not IL-12, during T cell activation. Activation of T cells with APC derived from the opposite sex demonstrated that these cytokines were derived from the respective APC populations. Furthermore, inhibition of IL-10, but not TGF-beta, during T cell activation resulted in the secretion of IL-12 by male-derived APC. APC from naive male mice, in which IL-10 was reduced in vivo before isolation, also secrete IL-12, demonstrating altered APC cytokine secretion was due to an environment high in IL-10 before Ag encounter. Finally, APC derived from castrated male mice preferentially secrete IL-12 during T cell activation. These data demonstrate a link between gonadal hormones and APC activity and suggest that these hormones alter the APC, thereby influencing cytokine secretion during initial T cell activation.
Wilcoxen
S C
SC
Department of Neurology and Animal Resources, Keck School of Medicine, University of Southern California, Los Angeles 90033, USA.
Kirkman
E
E
Dowdell
K C
KC
Stohlman
S A
SA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008213:Lymphocyte Activation; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009919:Orchiectomy; D012727:Sex Characteristics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016753:Interleukin-10; D018664:Interleukin-12