title: Biological functions of Mycobacterium tuberculosis-specific CD4+T cells were impaired by tuberculosis pleural fluid.
abstract: The local milieu at the site of Mycobacterium tuberculosis infection that modulates T-cell functions is the main battleground for the host to build counter-M. tuberculosis immune responses. CD4+T cells are enriched predominantly in tuberculosis pleurisy and their roles are of considerable importance, but their nature and functional profiles linked with local condition remain elusive. Here we evaluated the functions of M. tuberculosis-specific CD4+T cells from the major three profiles: cytokines production, cell activation and division. Results showed that pleural fluid (PF) from tuberculosis patients in a dose dependent manner inhibited the production of IFN-γ, IL-2 and TNF-α by M. tuberculosis-specific peptides or BCG activated CD4+T cells from pleural fluid mononuclear cells (PFMCs). Surface staining for activation molecules indicated that PF could also blunt cell activation process. CFSE labeling showed that antigen-specific CD4+T cell division ceased following co-incubation with PF. Pre- or post-treatment with PF could disturb subsequent cell activities. The strong inhibitory effect mediated by PF on CD4+T cells was functional predominance. Moreover, application of inhibitors of IDO, adenosine, neutralizing Abs to IL-10 and TGF-β could partially reverse IFN-γ production. Our current research provided novel information that the functions of antigen-specific CD4+T cells coincubated with PF were apparently impaired, which were distinct from cells that cultured in fresh culture medium. We concluded that CD4+T cell mediated antigen-specific cellular immune response that occurred locally might be impaired by PF.
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, Key Laboratory of Tropical Disease Control Research of Ministry of Education, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Suihua
authors.initials: S
authors.lastname: Lao
authors.forename: Binyan
authors.initials: B
authors.lastname: Yang
authors.forename: Changyou
authors.initials: C
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D001826:Body Fluids / Q000737:chemistry* / Q000276:immunology* / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D014396:Tuberculosis, Pleural / Q000097:blood / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma