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Identification and characterization of IL-10/IFN-–producing effector-like T cells with regulatory function in human blood

Charité Research Centre for ImmunoSciences and German Rheumatism Research Center, Campus Charité Mitte, 10117 Berlin, Germany

CORRESPONDENCE Jens Geginat: geginat{at}drfz.de

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 , 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.

© 2009 Häringer et al.
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