The H2(b) haplotype modifies the production of pro-inflammatory cytokines: implications for immunopathology.
Congenic strains of mice which differ only in their H2 haplotype were used to examine the effects of MHC genes on production of pro-inflammatory cytokines, as we have shown previously that H2(b) mice produce low levels of T cell cytokines compared to congenic H2(k) and H2(d) mice. RNase protection assays were used to assess cytokine mRNA and cytokine protein was assessed by ELISA or bioassay. Concanavalin A or phorbol myristate acetate/calcium ionophore/anti-CD3 stimulation of spleen cells from H2(b) congenic mice induced less IL-1, IL-2, IFN-gamma and MIF mRNA and/or protein than the equivalent cells from H2(d) mice. However, following stimulation with lipopolysaccharide or phorbol myristate acetate/calcium ionophore, peritoneal cells from H2(b) mice synthesised significantly more IL-1 beta, TNF-alpha, TNFR and IFN-gamma protein and IFN-gamma mRNA than cells from congenic H2(k) or H2(d) mice. These differences were evident in congenic C57BL/10 and/or BALB/c strains. We suggest that the low IL-1 production in H2(b) spleen cultures is secondary to lower T cell activation. Evidence that the H2(b) haplotype carries an immunoregulatory allele which affects cytokine production warrants further investigation.
Matthews
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Department of Pathology, University of Western Australia, Perth, Western Australia, Australia. vancem@dci.uwa.edu.au
Price
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D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D064532:Histocompatibility Antigen H-2D; D007154:Immune System Diseases / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha