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.
Immunogenetics. 2011 Feb;63(2):95-102. doi: 10.1007/s00251-010-0492-6. Epub 2010 Nov 18.
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.
在给定的健康个体中，外周血 T 淋巴细胞及其两个主要亚群（CD4+CD8-和 CD4-CD8+）的数量变化不大，但个体之间存在很大差异。有人提出，这些计数可能受到 MHC 多态性的影响，因为 MHC 分子在胸腺 T 淋巴细胞成熟和向外周 T 淋巴细胞呈递抗原肽方面起着重要作用。为了验证这一假设，我们选择了食蟹猴（Macaca fascicularis）作为一种与人类进化关系密切的动物模型。我们选择菲律宾猕猴种群，是因为该岛猕猴种群的 MHC 多态性受到限制。使用自动分析仪计数外周血淋巴细胞，并通过免疫标记和流式细胞术评估 T 淋巴细胞亚群。使用分布在 MHC 和 DRB 基因座的 14 个微卫星标记，通过变性梯度凝胶电泳和测序对 200 个无关个体的 MHC 多态性进行了研究。所有标记均处于哈迪-温伯格平衡。使用 UNPHASED 软件测试等位基因关联。我们发现 MHC Ⅱ类区域对 CD4+T 淋巴细胞计数有显著影响，最大影响与结合 DRACA 等位基因 274 和 DRB 单倍型 #8a 的两个位点单倍型有关（p<8×10(-7)）。我们的数据应激发对人类 CD4+T 细胞计数的类似关联研究。
