Identification and characterization of IL-10/IFN-γ–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 γ, 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.