title: Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines.
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.
authors: Central Laboratory for Advanced Diagnostic and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy; Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Palermo, Italy.
authors: Nadia
authors: N
authors: Caccamo
authors: Gabriella
authors: G
authors: Pietra
authors: Lucy C
authors: LC
authors: Sullivan
authors: Andrew G
authors: AG
authors: Brooks
authors: Teresa
authors: T
authors: Prezzemolo
authors: Marco P
authors: MP
authors: La Manna
authors: Diana
authors: D
authors: Di Liberto
authors: Simone A
authors: SA
authors: Joosten
authors: Krista E
authors: KE
authors: van Meijgaarden
authors: Paola
authors: P
authors: Di Carlo
authors: Lucina
authors: L
authors: Titone
authors: Lorenzo
authors: L
authors: Moretta
authors: Maria C
authors: MC
authors: Mingari
authors: Tom H M
authors: TH
authors: Ottenhoff
authors: Francesco
authors: F
authors: Dieli
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D060085:Coinfection / Q000276:immunology / Q000382:microbiology / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology; D000097625:HLA-E Antigens
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000097625:HLA-E Antigens; C527060:Klrc2 protein, mouse
keywords: CD8 T lymphocytes; HLA-E; Mycobacterium tuberculosis; TB; Tetramers; Type 2 cytokines