title: Pulmonary TCR γδ T cells induce the early inflammation of granuloma formation by a glycolipid trehalose 6,6'-dimycolate (TDM) isolated from Mycobacterium tuberculosis.
abstract: We previously showed that formation of pulmonary granulomas in mice in response to a mycobacterial glycolipid, trehalose 6,6'-dimycolate (TDM) is due to the action of TNF-α and not of IFN-γ. However, the mechanisms of formation and maintenance of pulmonary granulomas are not yet clear. The purpose of the present study is to evaluate the mechanisms of granuloma formation by TDM at the early phase. Histological analysis showed that inflammatory cells infiltrated the murine pulmonary interstitium on day 2 after an intravenous injection with TDM as a w/o/w emulsion. Clear granuloma formation was observed on day 7 after the injection. The mRNA expression of IL-17, IFN-γ and macrophage inflammatory protein 2 was found in lung mononuclear cells at the day after TDM injection. The major IL-17-producing cells were T-cell receptor (TCR) γδ T cells expressing Vγ6. In mice depleted of γδ T cells by treatment with anti-TCR γδ monoclonal antibody, the number of TDM-induced granuloma was decreased, but the size of granuloma was not affected. Our results suggest that the mycobacterial glycolipid TDM causes activation of IL-17-producing TCR γδ T cells and stimulates chemotaxis of inflammatory cells including neutrophils in to lung.
authors.affiliation: Department of Bioscience, Graduate School of Science, Kitasato University, Kitasato, Minami-ku, Sagamihara, Kanagawa, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Saitoh
authors.forename: Ikuya
authors.initials: I
authors.lastname: Yano
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kumazawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takimoto
mesh_terms: D000818:Animals; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D003311:Cord Factors / Q000633:toxicity*; D016207:Cytokines / Q000276:immunology; D005260:Female; D015769:Granuloma, Respiratory Tract / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
chemical_list: D003311:Cord Factors; D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta