Decreased IL-12 production underlies the decreased ability of male lymph node cells to induce experimental autoimmune encephalomyelitis.
Myelin basic protein (MBP)-specific T lymphocytes from male SJL mice were shown to be less encephalitogenic than MBP-specific T lymphocytes from females. Mechanisms underlying this gender difference in the induction phase of EAE were examined. Following immunization with MBP, draining lymph nodes contained fewer cells, and Ag-specific proliferative responses were decreased in males as compared with females. These gender differences in the proliferative response were not unique to MBP-specific responses since they were also observed after immunization with hen eggwhite lysozyme. Short-term MBP-specific T cell lines derived from females and males mapped with identical specificity, indicating no defect in the ability of male APCs to process Ag. Interestingly, IL-12 and IFN-gamma production was decreased following Ag-specific stimulation of draining lymph node cells (LNC) from males as compared with females, but IL-10 and IL-4 were no different. While male-derived LNCs were less encephalitogenic than female derived LNCs, cotransfer and coculture of male LNCs with female LNCs demonstrated that male LNCs were not immunosuppressive. Administration of IL-12 to LNCs from male mice enhanced encephalitogenicity. These data indicate that deficient endogenous IL-12 production within draining LNCs of male SJL mice is central to gender differences in the induction phase of experimental autoimmune encephalomyelitis.
Kim
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Multiple Sclerosis Center, Department of Neurology, University of California, Los Angeles 90095, USA.
Voskuhl
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RR
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D007114:Immunization; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D012727:Sex Characteristics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000276:Adjuvants, Immunologic; D000939:Epitopes; D004676:Myelin Basic Protein; D018664:Interleukin-12; D007371:Interferon-gamma