title: Mechanisms of augmented resistance of cyclosporin A-treated mice to influenza virus infection by trehalose-6,6'-dimycolate.
abstract: Cyclosporin A (CsA), which is an immunosuppressive drug of helper T lymphocytes, diminished a resistance of mice to influenza virus infection. Mice inoculated intravenously with trehalose-6,6'-dimycolate (TDM, a glycolipid component of the cell wall of Mycobacterium) in an oil-in-water emulsion (TDM emulsion) recovered the resistance to influenza virus infection impaired by CsA. Number of antibody-producing cells was markedly reduced in CsA- and/or TDM-treated mice. Interferon production in lung of TDM-treated mice was augmented; however, it was extremely reduced not only in CsA-treated mice, but also in CsA- and TDM-treated mice. Activities of natural killer cells of CsA- and/or TDM-treated mice were not different from that of control mice. Numbers of lymphocytes in lung of TDM-treated mice and CsA- and TDM-treated mice were more predominantly increased than that of control mice. Analysis of lung lymphocytes by flow cytometry revealed no difference between the populations of L3T4+ T lymphocytes and Lyt-2.2+ T lymphocytes in CsA- and/or TDM-treated mice and the populations in control mice. However, the population of gamma delta T cell receptor positive (gamma delta TCR+) lymphocytes increased markedly in lung of TDM-treated mice and also CsA- and TDM-treated mice. In vitro experiments showed that macrophage cultures treated with TDM emulsion released a mediator(s) which activates T lymphocytes, but not B lymphocytes. These and our earlier results suggest that the recovered anti-influenza virus resistance of CsA-treated mice by treatment with TDM emulsion was caused by elicitation of macrophages with TDM, then activation of T lymphocytes, especially gamma delta TCR+ lymphocytes.
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000921:Antibody-Producing Cells / Q000276:immunology; D002478:Cells, Cultured; D003311:Cord Factors / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D009980:Influenza A virus / Q000276:immunology; D007275:Injections, Intravenous; D007372:Interferons / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D003311:Cord Factors; D016572:Cyclosporine; D007372:Interferons