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Human MAIT and CD8 alpha alpha cells develop from a pool of type-17 precommitted CD8(+) T cells

  • LJ Walker
  • , YH Kang
  • , MO Smith
  • , H Tharmalingham
  • , N Ramamurthy
  • , VM Fleming
  • , N Sahgal
  • , A Leslie
  • , Ye Htun Oo
  • , A Geremia
  • , TJ Scriba
  • , WA Hanekom
  • , GM Lauer
  • , O Lantz
  • , David Adams
  • , F Powrie
  • , E Barnes
  • , P Klenerman

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

Human mucosal associated invariant T (MAIT) CD8(+) and Tc17 cells are important tissue-homing cell populations, characterized by high expression of CD161 ((++)) and type-17 differentiation, but their origins and relationships remain poorly defined. By transcriptional and functional analyses, we demonstrate that a pool of polyclonal, precommitted type-17 CD161(++)CD8 alpha beta(+) T cells exist in cord blood, from which a prominent MAIT cell (TCR V alpha 7.2(+)) population emerges postnatally. During this expansion, CD8 alpha alpha T cells appear exclusively within a CD161(++)CD8(+)/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161(++)CD8 alpha beta(+) counterparts. Our data demonstrate the origin and differentiation pathway of MAIT-cells from a naive type-17 precommitted CD161(++)CD8(+) T-cell pool and the distinct phenotype and function of CD8 alpha alpha cells in man. (Blood. 2012;119(2):422-433)
Original languageEnglish
Pages (from-to)422-433
Number of pages12
JournalBlood
Volume119
Issue number2
DOIs
Publication statusPublished - 1 Jan 2012

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