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

Blood. 2007 Dec 1;110(12):3936-48. doi: 10.1182/blood-2007-04-083139. Epub 2007 Sep 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • CD3 Complex / biosynthesis
  • CD3 Complex / immunology*
  • CD4 Antigens / biosynthesis
  • CD4 Antigens / immunology*
  • CD8 Antigens / biosynthesis
  • CD8 Antigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / immunology
  • Gene Expression Regulation / immunology
  • Graft Survival / immunology*
  • HLA Antigens / blood
  • HLA Antigens / immunology*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / blood
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology
  • Kidney Transplantation / immunology*
  • L-Selectin / biosynthesis
  • L-Selectin / immunology
  • Liver Transplantation / immunology*
  • Male
  • Middle Aged
  • Transplantation Tolerance*

Substances

  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • L-Selectin
  • Interleukin-10