Identification and characterization of IL-10/IFN-gamma-producing effector-like T cells with regulatory function in human blood.
Two subsets of natural and adaptive regulatory T (T reg) cells have been described, but the identity of adaptive type 1 regulatory (Tr1)-like cells in humans is unclear. We analyzed a subset of human blood CD4(+) T cells--CD45RA(-)CD25(-)interleukin (IL)-7 receptor (R)(-) cells--that rapidly secreted high levels of IL-10 together with interferon gamma, but produced little IL-2. These IL-7R(-) T cells were rare, anergic, and largely Foxp3(-). They expressed low levels of Bcl-2 but high levels of Ki-67 and ICOS, suggesting that they have been recently activated in vivo. Consistently, they responded selectively to persistent foreign and self-antigens under steady-state conditions. Unlike natural CD25(+) T reg cells, IL-7R(-) cells suppressed naive and memory T cell proliferation in an IL-10-dependent fashion, and they required strong T cell receptor stimulation for suppression. To our knowledge, this is the first report that identifies Tr1-like cells in human blood. These IL-10-secreting cells have characteristics of chronically activated Th1 effector cells and are distinct from CD25(+) T reg cells.
Häringer
Barbara
B
Charité Research Centre for ImmunoSciences and German Rheumatism Research Center, Campus Charité Mitte, 10117 Berlin, Germany.
Lozza
Laura
L
Steckel
Bodo
B
Geginat
Jens
J
D015703:Antigens, CD / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D019672:Genes, T-Cell Receptor; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation; D054400:Receptors, CCR7 / Q000172:deficiency / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015703:Antigens, CD; D001324:Autoantigens; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D054400:Receptors, CCR7; D020395:Receptors, Interleukin-7; D016753:Interleukin-10; D007371:Interferon-gamma