Human anergic/suppressive CD4(+)CD25(+) T cells: a highly differentiated and apoptosis-prone population

Eur J Immunol. 2001 Apr;31(4):1122-31. doi: 10.1002/1521-4141(200104)31:4<1122::aid-immu1122>;2-p.


Anergic/suppressive CD4(+)CD25(+) T cells exist in animal models but their presence has not yet been demonstrated in humans. We have identified and characterized a human CD4(+)CD25(+) T cell subset, which constitutes 7-10 % of CD4(+) T cells in peripheral blood and tonsil. These cells are a CD45RO(+)CD45RB(low) highly differentiated primed T cell population that is anergic to stimulation. Depletion of this small subset from CD4(+) T cells significantly enhances proliferation by threefold in the remaining CD4(+)CD25(-) T cells, while the addition of isolated CD4(+)CD25(+) T cells to CD4(+)CD25(-) T cells significantly inhibits proliferative activity. Blocking experiments suggest that suppression is not mediated via IL-4, IL-10 or TGF-beta and is cell-contact dependent. Isolated CD4(+)CD25(+) T cells are susceptible to apoptosis that is associated with low Bcl-2 expression, but this death can be prevented by IL-2 or fibroblast-secreted IFN-beta. However, the anergic/suppressive state of these cells is maintained after cytokine rescue. These human regulatory cells are therefore a naturally occurring, highly suppressive, apoptosis-prone population which are at a late stage of differentiation. Further studies into their role in normal and pathological situations in humans are clearly essential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis* / drug effects
  • CD4 Antigens / immunology*
  • CD4 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Communication
  • Cell Differentiation
  • Cell Separation
  • Cells, Cultured
  • Clonal Anergy / immunology*
  • Coculture Techniques
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Immunosuppression*
  • Interferon-beta / pharmacology
  • Interleukin-10 / analysis
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / immunology
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology
  • Interleukin-4 / analysis
  • Interleukin-4 / immunology
  • Palatine Tonsil / immunology
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Receptors, Interleukin-2 / immunology*
  • Receptors, Interleukin-2 / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / immunology
  • bcl-X Protein
  • fas Receptor / analysis


  • BCL2L1 protein, human
  • CD4 Antigens
  • Interleukin-2
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin-2
  • Transforming Growth Factor beta
  • bcl-X Protein
  • fas Receptor
  • Interleukin-10
  • Interleukin-4
  • Interferon-beta