Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines

Nadia Caccamo, Gabriella Pietra, Lucy C. Sullivan, Andrew G. Brooks, Teresa Prezzemolo, Marco P. La Manna, Diana Di liberto, Simone A. Joosten, Krista E. van Meijgaarden, Paola Di Carlo, Lucina Titone, Lorenzo Moretta, Maria C. Mingari, Tom H M Ottenhoff, Francesco Dieli

Research output: Contribution to journalArticlepeer-review

Abstract

CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB.

Original languageEnglish
Pages (from-to)1069-1081
Number of pages13
JournalEuropean Journal of Immunology
Volume45
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Keywords

  • CD8 T lymphocytes
  • HLA-E
  • Mycobacterium tuberculosis
  • TB
  • Tetramers
  • Type 2 cytokines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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