title: Regulation of acquired immunity by gamma delta T-cell/dendritic-cell interactions.
abstract: In humans, innate immune recognition of mycobacteria, including Mycobacterium tuberculosis and Mycobacterium leprae, involves toll-like receptor-2 (TLR-2), expressed on immature dendritic cells (DCs), and the T-cell gammadelta receptor expressed by a subpopulation of T cells that utilize Vdelta2 (Vdelta2 T cells). To investigate modulatory relationships between these host-cell populations in a microbial context, in vitro experiments were performed with human DCs and Vdelta2 T cells stimulated with model TLR-2 ligands and phosphoantigens, respectively. We observed that TLR-2-stimulated DCs enhanced interferon-gamma (IFN-gamma) production by Vdelta2 T cells; conversely, activated Vdelta2 T cells enhanced TLR-2-induced DC maturation via soluble factors including IFN-gamma, which costimulated interleukin-12 (IL-12) p70 secretion by DCs. Exposure of DCs to activated Vdelta2 T cells was critical for Th1 T-cell priming when TLR-2 stimulation was limiting. These results suggest that Vdelta2 T cells may play an adjuvant role in priming protective antimycobacterial immunity when TLR-2 stimulation is lacking, as may occur if the infectious inoculum is small, or if the pathogen is an intrinsically weak activator of DCs.
authors.affiliation: The Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Niraj
authors.initials: N
authors.lastname: Shrestha
authors.forename: James A
authors.initials: JA
authors.lastname: Ida
authors.forename: A Steven
authors.initials: AS
authors.lastname: Lubinski
authors.forename: Maria
authors.initials: M
authors.lastname: Pallin
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.forename: Patrick A J
authors.initials: PA
authors.lastname: Haslett
mesh_terms: D000328:Adult; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007110:Immunity, Active; D008213:Lymphocyte Activation / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism / Q000502:physiology
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2