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Eur J Immunol. 2015 Apr;45(4):1069-81. doi: 10.1002/eji.201445193. Epub 2015 Feb 17.

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

Author information

1
Central Laboratory for Advanced Diagnostic and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy; Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Palermo, Italy.

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.

KEYWORDS:

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

PMID:
25631937
DOI:
10.1002/eji.201445193
[Indexed for MEDLINE]
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