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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
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    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.
Language
  • English
Classification
Medicine
License
License undefined
Identifiers
  • RERO DOC 324215
  • ARK ark:/12658/srd1318954
Persistent URL
https://n2t.net/ark:/12658/srd1318954
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