Impact of MHC class II polymorphism on blood counts of CD4+ T lymphocytes in macaque

Abstract

While the number of peripheral blood T lymphocytes and of their two main subsets (CD4+CD8- and CD4-CD8+) varies little in a given healthy individual, substantial variation is observed between individuals. It was proposed that these counts could be influenced by MHC polymorphisms because of the well-established role of MHC molecules in thymic T lymphocyte maturation and presentation of antigenic peptides to peripheral T lymphocytes. To test this hypothesis, we have chosen the crab-eating macaque (Macaca fascicularis), an animal model phylogenetically close to man. We selected the Philippine macaque population because of a restriction of the MHC polymorphism in this islander population. Peripheral blood lymphocytes were counted with an automated analyzer and T lymphocyte subsets were assessed by immunolabeling and flow cytometry. The MHC polymorphism was investigated in 200 unrelated subjects using 14 microsatellites markers distributed across the MHC and the DRB locus that was genotyped by denaturing gradient gel electrophoresis and sequencing. All markers were in Hardy-Weinberg equilibrium. Allelic associations were tested with the UNPHASED software. We revealed a significant influence of the MHC class II region on CD4+ T lymphocyte blood count with the largest effect associated with a two-locus haplotypes combining the DRACA allele 274 and the DRB haplotype #8a (p < 8 × 10(-7)). Our data should stimulate a similar association study of the CD4+ T cell counts in humans.