Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive activity in vitro

Eur J Immunol. 2001 Apr;31(4):1247-54. doi: 10.1002/1521-4141(200104)31:4<1247::aid-immu1247>;2-m.


CD4(+)CD25(+) T cells in mice and rats are capable of transferring protection against organ-specific autoimmune disease and colitis and suppressing the proliferation of other T cells after polyclonal stimulation in vitro. Here we describe the existence in humans of CD4(+)CD25(+) T cells with the same in vitro characteristics. CD4(+)CD8(-)CD25(+) T cells are present in both the thymus and peripheral blood of humans ( approximately 10 % of CD4(+)CD8(-) T cells), proliferate poorly in response to mitogenic stimulation and suppress the proliferation of CD4(+)CD25(-) cells in co-culture. This suppression requires cell contact and can be overcome by the addition of exogenous IL-2. CD4(+)CD25(+) cells from thymus and blood were poor producers of IL-2 and IFN-gamma, and suppressed the levels of these cytokines produced by CD4(+)CD25(-) cells. However, CD4(+)CD25(+) PBL produced higher levels of IL-4 and similar amounts of IL-10 as CD4(+)CD25(-) cells. Regulatory CD4(+)CD25(+) T cells have an activated phenotype in the thymus with expression of CTLA-4 and CD122 (IL-2Rbeta). The fact that CD4(+)CD25(+) regulatory T cells are present with a similar frequency in the thymus of humans, rats and mice, suggests that the role of these cells in the maintenance of immunological tolerance is an evolutionarily conserved mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmunity / immunology
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Communication / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Flow Cytometry
  • Humans
  • Immune Tolerance / immunology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Ionomycin / pharmacology
  • Lymphocyte Activation / drug effects
  • Mitogens / immunology
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thymus Gland / cytology*
  • Thymus Gland / drug effects
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism


  • CD4 Antigens
  • Interleukin-2
  • Mitogens
  • Receptors, Interleukin-2
  • Interleukin-10
  • Ionomycin
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate