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Blood, 1 December 2007, Vol. 110, No. 12, pp. 3936-3948.
Prepublished online as a Blood First Edition Paper on September 5, 2007; DOI 10.1182/blood-2007-04-083139.


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IMMUNOBIOLOGY

CD3+CD4low and CD3+CD8low are induced by HLA-G: novel human peripheral blood suppressor T-cell subsets involved in transplant acceptance

Abderrahim Naji1, Solene Le Rond1, Antoine Durrbach2, Irene Krawice-Radanne1, Caroline Creput2, Marina Daouya1, Julien Caumartin1, Joel LeMaoult1, Edgardo D. Carosella1, and Nathalie Rouas-Freiss1

1 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, Institut Universitaire d'Hematologie (IUH), Paris; and 2 Departement de Nephrologie et Transplantation, Hopital du Kremlin-Bicetre, Le Kremlin-Bicetre, France

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+CD4low and CD3+CD8low 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+CD4low and CD3+CD8low 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+CD4low and CD3+CD8low 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.


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