title: CD3+CD4low and CD3+CD8low are induced by HLA-G: novel human peripheral blood suppressor T-cell subsets involved in transplant acceptance.
abstract: 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.
authors.affiliation: 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.
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Naji
authors.forename: Solene
authors.initials: S
authors.lastname: Le  Rond
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.forename: Irene
authors.initials: I
authors.lastname: Krawice-Radanne
authors.forename: Caroline
authors.initials: C
authors.lastname: Creput
authors.forename: Marina
authors.initials: M
authors.lastname: Daouya
authors.forename: Julien
authors.initials: J
authors.lastname: Caumartin
authors.forename: Joel
authors.initials: J
authors.lastname: LeMaoult
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rouas-Freiss
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000096:biosynthesis / Q000276:immunology*; D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology*; D016827:CD8 Antigens / Q000096:biosynthesis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000097:blood / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D019041:L-Selectin / Q000096:biosynthesis / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D023001:Transplantation Tolerance