6533b7dbfe1ef96bd1270d31
RESEARCH PRODUCT
Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines
Marco Pio La MannaLorenzo MorettaMaria Cristina MingariSimone A. JoostenLucina TitonePaola Di CarloFrancesco DieliTeresa PrezzemoloNadia CaccamoTom H. M. OttenhoffKrista E. Van MeijgaardenDiana Di LibertoLucy C. SullivanAndrew G. BrooksGabriella Pietrasubject
MaleTetramersCytotoxicHLA-EReceptors Antigen T-Cell alpha-betaT-LymphocytesEpitopes T-LymphocyteHIV InfectionsMycobacterium tuberculosiEpitopesHLA-EReceptorsImmunology and AllergyCells CulturedType 2 cytokinealpha-betaCulturedbiologyCoinfectionType 2 cytokinesMedicine (all)BacterialMiddle AgedAcquired immune systemAntibodies Bacterialmedicine.anatomical_structureTBAntigenCytokinesFemaleNK Cell Lectin-Like Receptor Subfamily CNK Cell Lectin-Like Receptor Subfamily DCD8 T lymphocyteProtein BindingAdultTuberculosisSettore MED/17 - Malattie InfettiveT cellCellsImmunologyAntibodiesMycobacterium tuberculosisImmune systemAntigenMHC class ImedicineHumansTuberculosisAntigensSettore MED/04 - Patologia GeneraleAntigens BacterialCD8 T lymphocytes; HLA-E; Mycobacterium tuberculosis; TB; Tetramers; Type 2 cytokines; Adult; Antibodies Bacterial; Antigens Bacterial; Cells Cultured; Coinfection; Cytokines; Epitopes T-Lymphocyte; Female; HIV Infections; Histocompatibility Antigens Class I; Humans; Male; Middle Aged; Mycobacterium tuberculosis; NK Cell Lectin-Like Receptor Subfamily C; NK Cell Lectin-Like Receptor Subfamily D; Protein Binding; Receptors Antigen T-Cell alpha-beta; T-Lymphocytes Cytotoxic; Tuberculosis; Immunology; Immunology and Allergy; Medicine (all)Histocompatibility Antigens Class IMycobacterium tuberculosismedicine.diseasebiology.organism_classificationT-CellVirologyCD8 T lymphocytesT-LymphocyteImmunologybiology.proteinTetramerT-Lymphocytes CytotoxicCD8 T lymphocytes; HLA-E; Mycobacterium tuberculosis; TB; Tetramers; Type 2 cytokines; Immunology; Immunology and Allergydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-04-30 |