Submitted April 2, 2007
Accepted July 29, 2007
CD3+CD4low and CD3+CD8low are induced by HLA-G: novel human peripheral blood suppressor T cell subsets involved in transplant acceptance
Abderrahim Naji, Solene Le Rond, Antoine Durrbach, Irene Krawice-Radanne, Caroline Creput, Marina Daouya, Julien Caumartin, Joel LeMaoult, Edgardo D Carosella, and Nathalie Rouas-Freiss*
Service de Recherches en Hemato-Immunologie, CEA-DSV-DRM, Hopital Saint-Louis, IUH, Paris, France
Departement de Nephrologie et Transplantation, Hopital du Kremlin-Bicetre, Le Kremlin-Bicetre, France
* Corresponding author; email: nathalie.rouas-freiss{at}cea.fr.
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 transplanted patients. 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 post-translational 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. Also, these HLA-G-induced CD3+CD4low and CD3+CD8low subpopulations are Foxp3-negative suppressor T cells whose function involves IL-10. Biological relevance came from analysis of transplanted patients 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 to HLA-G-negative transplanted patients and healthy individuals. These data define novel immunosuppressive subpopulations of peripheral blood T cells induced by HLA-G with potent implications in peripheral tolerance.
