Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties

Eva Billerbeck, Yu Hoi Kang, Lucy Walker, Helen Lockstone, Stefanie Grafmueller, Vicki Fleming, Jonathan Flint, Chris B. Willberg, Bertram Bengsch, Bianca Seigel, Narayan Ramamurthy, Nicole Zitzmann, Eleanor J. Barnes, Jonarthan Thevanayagam, Anisha Bhagwanani, Alasdair Leslie, Ye H. Oo, Simon Kollnberger, Paul Bowness, Oliver DrognitzDavid H. Adams, Hubert E. Blum, Robert Thimme, Paul Klenerman

Research output: Contribution to journalArticlepeer-review

214 Scopus citations

Abstract

CD8+ T lymphocytes play a key role in host defense, in particular against important persistent viruses, although the critical functional properties of such cells in tissue are not fully defined.Wehave previously observed that CD8+ T cells specific for tissue-localized viruses such as hepatitis C virus express high levels of the C-type lectin CD161. To explore the significance of this, we examined CD8 +CD161+ T cells in healthy donors and those with hepatitis C virus and defined a population of CD8+ T cells with distinct homing and functional properties. These cells express high levels of CD161 and a pattern of molecules consistent with type 17 differentiation, including cytokines (e.g., IL-17, IL-22), transcription factors (e.g., retinoic acid-related orphan receptor γ-t, P = 6 × 10-9; RUNX2, P = 0.004), cytokine receptors (e.g., IL-23R, P = 2 × 10-7; IL-18 receptor, P = 4 × 10-6), and chemokine receptors (e.g., CCR6, P = 3 × 10-8; CXCR6, P = 3 × 10-7; CCR2, P = 4 × 10-7). CD161+CD8+ T cells were markedly enriched in tissue samples and coexpressed IL-17 with high levels of IFN-γ and/or IL-22. The levels of polyfunctional cells in tissue was most marked in those with mild disease (P = 0.0006). These data define a T cell lineage that is present already in cord blood and represents as many as one in six circulating CD8+ T cells in normal humans and a substantial fraction of tissue-infiltrating CD8+ T cells in chronic in.ammation. Such cells play a role in the pathogenesis of chronic hepatitis and arthritis and potentially in other infectious and inflammatory diseases of man.

Original languageEnglish (US)
Pages (from-to)3006-3011
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number7
DOIs
StatePublished - Feb 16 2010
Externally publishedYes

Keywords

  • Arthritis
  • Hepatitis
  • Hepatitis C virus
  • IL-17
  • IL-22

ASJC Scopus subject areas

  • General

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