T cell suppression by naturally occurring HLA-G-expressing regulatory CD4+ T cells is IL-10-dependent and reversible

J Leukoc Biol. 2009 Aug;86(2):273-81. doi: 10.1189/jlb.1008649. Epub 2009 Apr 28.


CD4(+) T cells constitutively expressing the immune-tolerogenic HLA-G have been described recently as a new type of nT(reg) (HLA-G(pos) T(reg)) in humans. HLA-G(pos) T(reg) accumulate at sites of inflammation and are potent suppressors of T cell proliferation in vitro, suggesting their role in immune regulation. We here characterize the mechanism of how CD4(+) HLA-G(pos) T(reg) influence autologous HLA-G(neg) T(resp) function. Using a suppression system free of APC, we demonstrate a T-T cell interaction, resulting in suppression of HLA-G(neg) T(resp), which is facilitated by TCR engagement on HLA-G(pos) T(reg). Suppression is independent of cell-cell contact and is reversible, as the removal of HLA-G(pos) T(reg) from the established coculture restored the proliferative capability of responder cells. Further, HLA-G(pos) T(reg)-mediated suppression critically depends on the secretion of IL-10 but not TGF-beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Adhesion / immunology
  • Cell Communication / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Down-Regulation / immunology
  • Female
  • HLA Antigens / metabolism*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immune Tolerance / physiology*
  • Interleukin-10 / metabolism*
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Young Adult


  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • IL10 protein, human
  • Transforming Growth Factor beta
  • Interleukin-10