Naji Abderrahim, Le Rond Solene, Durrbach Antoine, Krawice-Radanne Irene, Creput Caroline, Daouya Marina, Caumartin Julien, LeMaoult Joel, Carosella Edgardo D, Rouas-Freiss Nathalie
Service de Recherches en Hemato-Immunologie, Commissariat à l'energie atomique-Direction des science, du vivant-Departement de la recherche medical (CEA-DSV-DRM), Hopital Saint-Louis, Paris, France.
Blood. 2007 Dec 1;110(12):3936-48. doi: 10.1182/blood-2007-04-083139. Epub 2007 Sep 5.
HLA-G is a tolerogenic molecule whose detection in sera and within allografted tissues is associated with better graft acceptance. HLA-G mediates T-cell differentiation into suppressor cells, which are thought to promote tolerance. Here, we investigated such T cells phenotypically and functionally and assessed their clinical relevance in the peripheral blood of patients who have undergone transplantation. Our results demonstrate that HLA-G expressed by antigen-presenting cells or present as soluble protein down-regulates the expression of CD4 and CD8 on allostimulated T cells at both transcriptional and posttranslational levels. These CD3(+)CD4(low) and CD3(+)CD8(low) T-cell subsets are characterized by an increased proportion of cells expressing CD45RA and HLA-DR, and a decreased number of cells expressing CD62L. In addition, these HLA-G-induced CD3(+)CD4(low) and CD3(+)CD8(low) subpopulations are Foxp3-negative suppressor T cells whose function involves IL-10. Biologic relevance came from analysis of patients who underwent transplantation, with high HLA-G plasma concentrations associated with better graft survival. Peripheral blood from these patients contains increased levels of IL-10 concomitantly to an enhanced representation of CD3(+)CD4(low) and CD3(+)CD8(low) T cells compared with HLA-G-negative patients who underwent transplantation and healthy individuals. These data define novel immunosuppressive subpopulations of peripheral blood T cells induced by HLA-G with potent implications in peripheral tolerance.
HLA - G是一种具有免疫耐受原性的分子，在血清和同种异体移植组织中检测到该分子与更好的移植物接受度相关。HLA - G介导T细胞分化为抑制性细胞，据认为这些抑制性细胞可促进免疫耐受。在此，我们对外周血中此类T细胞进行了表型和功能研究，并评估了它们在接受移植患者外周血中的临床相关性。我们的结果表明，由抗原呈递细胞表达或作为可溶性蛋白存在的HLA - G在转录和翻译后水平下调同种异体刺激的T细胞上CD4和CD8的表达。这些CD3(+)CD4(low)和CD3(+)CD8(low) T细胞亚群的特征是表达CD45RA和HLA - DR的细胞比例增加，而表达CD62L的细胞数量减少。此外，这些由HLA - G诱导的CD3(+)CD4(low)和CD3(+)CD8(low)亚群是Foxp3阴性抑制性T细胞，其功能涉及IL - 10。通过对接受移植患者的分析发现了生物学相关性，高血浆HLA - G浓度与更好的移植物存活相关。与接受移植的HLA - G阴性患者和健康个体相比，这些患者外周血中IL - 10水平升高，同时CD3(+)CD4(low)和CD3(+)CD8(low) T细胞的比例增加。这些数据定义了由HLA - G诱导的外周血T细胞新型免疫抑制亚群，对外周免疫耐受具有重要意义。
