CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function

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

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Journal article

CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function

Rivino, Laura Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Charité Research Center for ImmunoSciences and German Rheumatism Research Center, Campus Charité Mitte, 10117 Berlin, Germany
Gruarin, Paola Istituto Nazionale di Genetica Molecolare, 20122 Milan, Italy
Häringer, Barbara Charité Research Center for ImmunoSciences and German Rheumatism Research Center, Campus Charité Mitte, 10117 Berlin, Germany
Steinfelder, Svenja Charité Research Center for ImmunoSciences and German Rheumatism Research Center, Campus Charité Mitte, 10117 Berlin, Germany
Lozza, Laura Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Charité Research Center for ImmunoSciences and German Rheumatism Research Center, Campus Charité Mitte, 10117 Berlin, Germany
Steckel, Bodo Charité Research Center for ImmunoSciences and German Rheumatism Research Center, Campus Charité Mitte, 10117 Berlin, Germany
Weick, Anja Charité Research Center for ImmunoSciences and German Rheumatism Research Center, Campus Charité Mitte, 10117 Berlin, Germany
Sugliano, Elisa Istituto Nazionale di Genetica Molecolare, 20122 Milan, Italy
Jarrossay, David Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Kühl, Anja A. Charité Research Center for ImmunoSciences/Institute of Pathology, Campus Benjamin Franklin, 12200 Berlin, Germany
Loddenkemper, Christoph Charité Research Center for ImmunoSciences/Institute of Pathology, Campus Benjamin Franklin, 12200 Berlin, Germany - Institute of Pathology, Technische Universität München, 81625 Munich, Germany
Abrignani, Sergio Istituto Nazionale di Genetica Molecolare, 20122 Milan, Italy
Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Geginat, Jens Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Charité Research Center for ImmunoSciences and German Rheumatism Research Center, Campus Charité Mitte, 10117 Berlin, Germany - Istituto Nazionale di Genetica Molecolare, 20122 Milan, Italy

01.03.2010

Published in:

Journal of experimental medicine. - 2010, vol. 207, no. 3, p. 565-577

English 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.

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