title: Identification of a CD4+CD25+ T cell subset committed in vivo to suppress antigen-specific T cell responses without additional stimulation.
abstract: Naturally occurring CD4+ regulatory T cells can be identified on the basis of expression of CD25 and suppression of T cell responses in vitro after TCR triggering. Here, we demonstrate that a CD134+ subset of CD4+CD25+ T cells in naive rats suppresses antigen-specific T cell responses in vitro without additional TCR stimulation. In contrast, CD4+CD25+CD134- regulatory T cells and total CD4+CD25+ regulatory T cells have suppressive activity only during simultaneous activation of responder and regulatory T cells or after in vitro pre-activation. Furthermore CD4+CD25+CD134+ T cells have a more activated phenotype than CD4+CD25+CD134- T cells, as based on the expression of CD62L, CD45RC, and MHC class II. We propose that the CD134+ regulatory T cells contain an in vivo activated and highly suppressive regulatory T cell subset. CD4+CD25+CD134+ T cells can be found in several compartments of the immune system, including spleen, lymph nodes, and blood. Interestingly though, the relative amounts of these cells within the CD4+ population and their CD134 expression levels are highest in mucosa-draining lymph nodes and lowest in blood. This suggests that the presence of CD4+CD25+CD134+ T cells indicates sites of active immune suppression.
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Esther N M
authors.initials: EN
authors.lastname: Nolte-'t Hoen
authors.forename: Josée P A
authors.initials: JP
authors.lastname: Wagenaar-Hilbers
authors.forename: Elmieke P J
authors.initials: EP
authors.lastname: Boot
authors.forename: Chia-Huey
authors.initials: CH
authors.lastname: Lin
authors.forename: Ger J A
authors.initials: GJ
authors.lastname: Arkesteijn
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: Leonie S
authors.initials: LS
authors.lastname: Taams
authors.forename: Marca H M
authors.initials: MH
authors.lastname: Wauben
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505718:Tnfrsf4 protein, rat