title: Human anergic/suppressive CD4(+)CD25(+) T cells: a highly differentiated and apoptosis-prone population.
abstract: 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.
authors: Department of Clinical Immunology, Royal Free and University College Medical School, London, GB.
authors: L S
authors: LS
authors: Taams
authors: J
authors: J
authors: Smith
authors: M H
authors: MH
authors: Rustin
authors: M
authors: M
authors: Salmon
authors: L W
authors: LW
authors: Poulter
authors: A N
authors: AN
authors: Akbar
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D018920:Coculture Techniques; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D016899:Interferon-beta / Q000494:pharmacology; D016753:Interleukin-10 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000032:analysis / Q000276:immunology; D014066:Palatine Tonsil / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology; D051020:bcl-X Protein; D019014:fas Receptor / Q000032:analysis
chemical_list: C494811:BCL2L1 protein, human; D015704:CD4 Antigens; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D051020:bcl-X Protein; D019014:fas Receptor; D016753:Interleukin-10; D015847:Interleukin-4; D016899:Interferon-beta