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

Laura Rivino, Paola Gruarin, Barbara Häringer, Svenja Steinfelder, Laura Lozza, Bodo Steckel, Anja Weick, Elisa Sugliano, David Jarrossay, Anja A Kühl, Christoph Loddenkemper, Sergio Abrignani, Federica Sallusto, Antonio Lanzavecchia, Jens Geginat

Research output: Contribution to journalArticle (Academic Journal)

Abstract

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)-beta. 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-gamma, 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.

Original languageEnglish
Pages (from-to)565-77
Number of pages13
JournalJournal of Experimental Medicine
Volume207
Issue number3
DOIs
Publication statusPublished - 15 Mar 2010

Keywords

  • CD4-Positive T-Lymphocytes/drug effects
  • Gene Expression Regulation
  • Homeostasis/immunology
  • Humans
  • Immunologic Memory
  • Immunosuppression
  • Interferon-gamma/genetics
  • Interleukin-10/biosynthesis
  • Interleukin-2/biosynthesis
  • Receptors, Antigen, T-Cell/immunology
  • Receptors, CCR6/genetics
  • T-Lymphocytes/drug effects
  • T-Lymphocytes, Regulatory/drug effects
  • Transforming Growth Factor beta/pharmacology

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  • Cite this

    Rivino, L., Gruarin, P., Häringer, B., Steinfelder, S., Lozza, L., Steckel, B., Weick, A., Sugliano, E., Jarrossay, D., Kühl, A. A., Loddenkemper, C., Abrignani, S., Sallusto, F., Lanzavecchia, A., & Geginat, J. (2010). CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function. Journal of Experimental Medicine, 207(3), 565-77. https://doi.org/10.1084/jem.20091021