MHC class II expression identifies functionally distinct human regulatory T cells

J Immunol. 2006 Apr 15;176(8):4622-31. doi: 10.4049/jimmunol.176.8.4622.

Abstract

It has been known for decades that circulating human CD4 cells can express functional MHC class II molecules that induce T cell nonresponsiveness with Ag presentation. Because there is significant expression of MHC class II (MHC-II) determinants (DR) on a subpopulation CD4+ CD25(high) regulatory T cells (Treg), we examined the function of CD4 cells expressing MHC-DR. We demonstrate that MHC-II expression on human CD4+ CD25(high) T cells identifies a functionally distinct population of Treg that induces early contact-dependent suppression that is associated with high Foxp3 expression. In striking contrast, MHC-II- CD4+ CD25(high) Treg induce early IL-4 and IL-10 secretion and a late Foxp3-associated contact-dependent suppression. The DR expressing CD25(high) Treg express higher levels of Foxp3 message and protein, compared with the DR- CD25(high) Treg population. Direct single-cell cloning of CD4+ CD25(high) Treg revealed that, regardless of initial DR expression, ex vivo expression of CD25(high), and not DR, predicted which clones would exhibit contact-dependent suppression, high levels of Foxp3 message, and an increased propensity to become constitutive for DR expression. Thus, the direct ex vivo expression of MHC-II in the context of CD25(high) identifies a mature, functionally distinct regulatory T cell population involved in contact-dependent in vitro suppression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / immunology
  • Forkhead Transcription Factors / genetics
  • Gene Expression
  • HLA-DR Antigens / metabolism
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • Immune Tolerance
  • In Vitro Techniques
  • Interleukin-10 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Receptors, Interleukin-2 / metabolism
  • T-Lymphocytes, Regulatory / classification*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II
  • IL10 protein, human
  • IL4 protein, human
  • Receptors, Interleukin-2
  • Interleukin-10
  • Interleukin-4