title: Mycobacterium-Specific γ9δ2 T Cells Mediate Both Pathogen-Inhibitory and CD40 Ligand-Dependent Antigen Presentation Effects Important for Tuberculosis Immunity.
abstract: Numerous pathogens, including Mycobacterium tuberculosis, can activate human γ9δ2 T cells to proliferate and express effector mechanisms. γ9δ2 T cells can directly inhibit the growth of intracellular mycobacteria and may also act as antigen-presenting cells (APC). Despite evidence for γδ T cells having the capacity to function as APC, the mechanisms involved and importance of these effects on overall tuberculosis (TB) immunity are unknown. We prepared M. tuberculosis-specific γ9δ2 T cell lines to study their direct protective effects and APC functions for M. tuberculosis-specific αβ T cells. The direct inhibitory effects on intracellular mycobacteria were measured, and the enhancing effects on proliferative and effector responses of αβ T cells assessed. Furthermore, the importance of cell-to-cell contact and soluble products for γ9δ2 T cell effector responses and APC functions were investigated. We demonstrate, in addition to direct inhibitory effects on intracellular mycobacteria, the following: (i) γ9δ2 T cells enhance the expansion of M. tuberculosis-specific αβ T cells and increase the ability of αβ T cells to inhibit intracellular mycobacteria; (ii) although soluble mediators are critical for the direct inhibitory effects of γ9δ2 T cells, their APC functions do not require soluble mediators; (iii) the APC functions of γ9δ2 T cells involve cell-to-cell contact that is dependent on CD40-CD40 ligand (CD40L) interactions; and (iv) fully activated CD4(+) αβ T cells and γ9δ2 T cells provide similar immune enhancing/APC functions for M. tuberculosis-specific T cells. These effector and helper effects of γ9δ2 T cells further indicate that these T cells should be considered important new targets for new TB vaccines.
authors.affiliation: Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA abateg@slu.edu hoftdf@slu.edu.
authors.forename: Getahun
authors.initials: G
authors.lastname: Abate
authors.affiliation: Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, Missouri, USA.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Spencer
authors.affiliation: Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA.
authors.forename: Fahreta
authors.initials: F
authors.lastname: Hamzabegovic
authors.affiliation: Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA.
authors.forename: Azra
authors.initials: A
authors.lastname: Blazevic
authors.affiliation: Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Xia
authors.affiliation: Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, Missouri, USA abateg@slu.edu hoftdf@slu.edu.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
mesh_terms: D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007156:Immunologic Memory; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand