Lymphocytes from H2 mice produce lower levels of several cytokines than congenic H2 or H2 mice.
Inbred mice of congenic strains that differ only in their H2 haplotype were used to examine the effects of MHC genes on production of cytokines. Spleen and lymph node cells were stimulated with mitogens in vitro, and cytokine protein was assessed by ELISA and/or bioassays. Cells from H2b mice synthesized less IL-3, IL-4, IL-5, TNF and IL-10 (less clearly) than the equivalent cells from H2k or H2d mice. Production of IL-6 by H2b spleen and lymph node cells was lower than that by cells from H2d mice. In addition, lower lymphoproliferative responses were observed in lymph node cultures from H2b mice. These effects were evident in congenic B10 and BALB strains. B10 H2b mice stimulated in vivo with anti-CD3 had lower levels of IFN-gamma and IL-5 protein in their serum compared with equivalent H2k and H2d mice. Because class I- or II-mediated antigen presentation was not required in our model, an immunoregulatory gene in the central MHC is implicated. Preliminary studies of MHC recombinant mice suggested that the gene or genes responsible lie telomeric of IEbeta. Evidence that the H2b haplotype carries an immunoregulatory allele with a small but consistent effect on cytokine production warrants further investigation.
Matthews
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VB
Department of Pathology, University of Western Australia and Royal Perth Hospital, Perth, Western Australia, Australia. vancem@dci.uwa.edu.au
Christiansen
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FT
Price
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D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis*; D006239:Haplotypes; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D007377:Interleukin-3 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008934:Mitogens; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D007377:Interleukin-3; D015848:Interleukin-5; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma