Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA‐E during active tuberculosis and express type 2 cytokines |
| |
Authors: | 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 Francesco Dieli |
| |
Institution: | 1. Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia;2. Central Laboratory for Advanced Diagnostic and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy;3. Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Palermo, Italy;4. Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands;5. Dipartimento di Medicina Clinica e delle Patologie Emergenti, Università di Palermo, Palermo, Italy;6. Istituto Giannina Gaslini, Genova, 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 |
|
|