Lymphocytes from H2b mice produce lower levels of several cytokines than congenic H2d or H2k mice

Abstract

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 H2^b mice synthesized less IL-3, IL-4, IL-5, TNF and IL-10 (less clearly) than the equivalent cells from H2^k or H2^d mice. Production of IL-6 by H2^b spleen and lymph node cells was lower than that by cells from H2^d mice. In addition, lower lymphoproliferative responses were observed in lymph node cultures from H2^b mice. These effects were evident in congenic B10 and BALB strains. B10 H2^b mice stimulated in vivo with anti-CD3 had lower levels of IFN-γ and IL-5 protein in their serum compared with equivalent H2^k and H2^d 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 IEβ. Evidence that the H2^b haplotype carries an immunoregulatory allele with a small but consistent effect on cytokine production warrants further investigation.