Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells

Eva V Acosta-Rodriguez, Laura Rivino, Jens Geginat, David Jarrossay, Marco Gattorno, Antonio Lanzavecchia, Federica Sallusto, Giorgio Napolitani

Research output: Contribution to journalArticle (Academic Journal)peer-review

1534 Citations (Scopus)

Abstract

Interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) have been characterized in mice as a distinct subset of effector cells, but their identity and properties in humans remain elusive. We report here that expression of CCR6 and CCR4 together identified human memory CD4+ T cells selectively producing IL-17 and expressing mRNA encoding the human ortholog of mouse RORgammat, a transcription factor, whereas CCR6 and CXCR3 identified T(H)1 cells producing interferon-gamma and T helper cells producing both interferon-gamma and IL-17. Memory T cells specific for Candida albicans were present mainly in the CCR6+CCR4+ T(H)-17 subset, whereas memory T cells specific for Mycobacterium tuberculosis were present in CCR6+CXCR3+ T helper type 1 subset. The elicitation of IL-17 responses correlated with the capacity of C. albicans hyphae to stimulate antigen-presenting cells for the priming of T(H)-17 responses in vitro and for the production of IL-23 but not IL-12. Our results demonstrate that human T(H)-17 cells have distinct migratory capacity and antigenic specificities and establish a link between microbial products, T helper cell differentiation and homing in response to fungal antigens.

Original languageEnglish
Pages (from-to)639-46
Number of pages8
JournalNature Immunology
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Animals
  • Antigens/immunology
  • Candida albicans/immunology
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • Immunologic Memory/immunology
  • Interleukin-17/biosynthesis
  • Interleukin-23/biosynthesis
  • Mice
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Phenotype
  • RNA, Messenger/genetics
  • Receptors, CCR4
  • Receptors, CCR6
  • Receptors, CXCR3
  • Receptors, Chemokine/metabolism
  • Receptors, Retinoic Acid/genetics
  • Receptors, Thyroid Hormone/genetics
  • T-Lymphocytes, Helper-Inducer/immunology

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