Rivino, Laura Gruarin, Paola Häringer, Barbara Steinfelder, Svenja Lozza, Laura Steckel, Bodo Weick, Anja Sugliano, Elisa Jarrossay, David Kühl, Anja A. Loddenkemper, Christoph Abrignani, Sergio Sallusto, Federica Lanzavecchia, Antonio Geginat, Jens 2010-03-01 Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10–producing memory T cells. Human CD4+CCR6+ memory T cells contained comparable numbers of IL-17– and IL-10–producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic T cell priming with transforming growth factor (TGF)–. In normal human spleens, the majority of CCR6+ memory T cells were in the close vicinity of CCR6+ myeloid dendritic cells (mDCs), and strikingly, some of them were secreting IL-10 in situ. Furthermore, CCR6+ memory T cells produced suppressive IL-10 but not IL-2 upon stimulation with autologous immature mDCs ex vivo, and secreted IL-10 efficiently in response to suboptimal T cell receptor (TCR) stimulation with anti-CD3 antibodies. However, optimal TCR stimulation of CCR6+ T cells induced expression of IL-2, interferon-, CCL20, and CD40L, and autoreactive CCR6+ T cell lines responded to various recall antigens. Notably, we isolated autoreactive CCR6+ T cell clones with context-dependent behavior that produced IL-10 with autologous mDCs alone, but that secreted IL-2 and proliferated upon stimulation with tetanus toxoid. We propose the novel concept that a population of memory T cells, which is fully equipped to participate in secondary immune responses upon recognition of a relevant recall antigen, contributes to the maintenance of tolerance under steady-state conditions. application/pdf https://susi.usi.ch/global/documents/318954 https://n2t.net/ark:/12658/srd1318954 https://susi.usi.ch/documents/318954/files/Rivino_JEM_2010.pdf eng info:eu-repo/semantics/altIdentifier/ark/12658/srd1318954 info:eu-repo/semantics/openAccess CC BY-NC-SA Journal of experimental medicine. - 2010, vol. 207, no. 3, p. 565-577 info:eu-repo/classification/udc/61 CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function http://purl.org/coar/resource_type/c_6501