Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells

Blood. 2012 Jan 12;119(2):422-33. doi: 10.1182/blood-2011-05-353789. Epub 2011 Nov 15.

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(++)CD8αβ(+) T cells exist in cord blood, from which a prominent MAIT cell (TCR Vα7.2(+)) population emerges post-natally. During this expansion, CD8αα T cells appear exclusively within a CD161(++)CD8(+)/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161(++)CD8αβ(+) 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 CD8αα cells in man.

Publication types

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

MeSH terms

  • Adult
  • Antigen Presentation
  • Biomarkers / metabolism
  • Blotting, Western
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Fetal Blood / immunology
  • Fetal Blood / metabolism
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Humans
  • Immunity, Mucosal / immunology*
  • Infant, Newborn
  • Oligonucleotide Array Sequence Analysis
  • Protein Isoforms
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Th17 Cells / cytology
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism

Substances

  • Biomarkers
  • CD8 Antigens
  • Cytokines
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Antigen, T-Cell