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

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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.

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Acknowledgments

We are pleased to thank Béatrice Atlan, Audrey Dauba, Stéphanie Despiau-Schiavinato, and Sylvie Hébrard for their excellent technical assistance. We thank Eric André (Bioprim, Baziège France) and Marc Bigaud (Novartis, Bâle) for their help in obtaining macaque blood samples.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratoire d’Immunogénétique Moléculaire, EA 3034, Faculté de Médecine Purpan, Université Paul Sabatier, Toulouse 3, IFR150 (INSERM), CHU de Toulouse, 1 avenue Jean Poulhes, TSA 50032, 31059, Toulouse cedex 9, France

    Alice Aarnink, Bénédicte Puissant-Lubrano, Marie Blancher-Sardou, Pol-André Apoil & Antoine Blancher

  2. Department of Immunology, INSERM U1016 and Université Paris Descartes, Institut Cochin, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France

    Henri-Jean Garchon

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  1. Alice Aarnink
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  2. Henri-Jean Garchon
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  3. Bénédicte Puissant-Lubrano
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  4. Marie Blancher-Sardou
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  5. Pol-André Apoil
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  6. Antoine Blancher
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Correspondence to Antoine Blancher.

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Table S1

Primers used to amplify the 18 microsatellites (DOC 59 kb)

Table S2

Allele polymorphism at 16 MHC microsatellites in the Philippine macaque population sample (DOC 57 kb)

Table S3

Allelic frequencies of 14 MHC markers in the Philippine population sample (n = 200) of Macaca fascicularis (DOC 290 kb)

Fig. S1

Correlation between Log CD4+ and Log lymphocytes and calculation of the residual values of Log CD4+. (DOC 59 kb)

Fig. S2

Description of DRB haplotypes in the Philippine cynomolgus macaques (DOC 67 kb)

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Aarnink, A., Garchon, HJ., Puissant-Lubrano, B. et al. Impact of MHC class II polymorphism on blood counts of CD4+ T lymphocytes in macaque. Immunogenetics 63, 95–102 (2011). https://doi.org/10.1007/s00251-010-0492-6

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  • DOI: https://doi.org/10.1007/s00251-010-0492-6

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