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

Nat Immunol. 2007 Jun;8(6):639-46. doi: 10.1038/ni1467. Epub 2007 May 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • T-Lymphocytes, Helper-Inducer / metabolism*

Substances

  • Antigens
  • CCR4 protein, human
  • CCR6 protein, human
  • CXCR3 protein, human
  • Ccr4 protein, mouse
  • Cxcr3 protein, mouse
  • Interleukin-17
  • Interleukin-23
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Messenger
  • RORC protein, human
  • Receptors, CCR4
  • Receptors, CCR6
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse