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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. This Article Full Text (PDF) All Versions of this Article: blood-2007-04-083139v1 110/12/3936    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Naji, A. Articles by Rouas-Freiss, N. Search for Related Content PubMed PubMed Citation Articles by Naji, A. Articles by Rouas-Freiss, N. Social Bookmarking                   What's this?  Previous Article  |  Next Article  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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Flajollet, I. Poras, E. D. Carosella, and P. Moreau RREB-1 Is a Transcriptional Repressor of HLA-G J. Immunol., December 1, 2009; 183(11): 6948 - 6959. [Abstract] [Full Text] [PDF] R. Bahri, A. Naji, C. Menier, B. Charpentier, E. D. Carosella, N. Rouas-Freiss, and A. Durrbach Dendritic Cells Secrete the Immunosuppressive HLA-G Molecule upon CTLA4-Ig Treatment: Implication in Human Renal Transplant Acceptance J. Immunol., December 1, 2009; 183(11): 7054 - 7062. [Abstract] [Full Text] [PDF] M.-Y. Cai, Y.-F. Xu, S.-J. Qiu, M.-J. Ju, Q. Gao, Y.-W. Li, B.-H. Zhang, J. Zhou, and J. Fan Human Leukocyte Antigen-G Protein Expression Is an Unfavorable Prognostic Predictor of Hepatocellular Carcinoma following Curative Resection Clin. Cancer Res., July 15, 2009; 15(14): 4686 - 4693. [Abstract] [Full Text] [PDF] E. D. Carosella, B. Favier, N. Rouas-Freiss, P. Moreau, and J. LeMaoult Beyond the increasing complexity of the immunomodulatory HLA-G molecule Blood, May 15, 2008; 111(10): 4862 - 4870. [Abstract] [Full Text] [PDF]

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