Biological functions of Mycobacterium tuberculosis-specific CD4+T cells were impaired by tuberculosis pleural fluid

Immunol Lett. 2011 Aug 30;138(2):113-21. doi: 10.1016/j.imlet.2011.03.008. Epub 2011 Apr 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Antibodies, Neutralizing / pharmacology
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism
  • Antigens, Bacterial / pharmacology*
  • Bacterial Proteins / immunology
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / pharmacology*
  • Body Fluids / chemistry*
  • Body Fluids / immunology*
  • Body Fluids / microbiology
  • CD4-Positive T-Lymphocytes* / cytology
  • CD4-Positive T-Lymphocytes* / drug effects
  • CD4-Positive T-Lymphocytes* / immunology
  • CD4-Positive T-Lymphocytes* / metabolism
  • Cells, Cultured
  • Female
  • Humans
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology
  • Interleukin-2 / antagonists & inhibitors
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Lung / immunology*
  • Lung / microbiology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Monocytes / cytology
  • Monocytes / immunology
  • Monocytes / metabolism
  • Mycobacterium tuberculosis / growth & development
  • Mycobacterium tuberculosis / immunology
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / immunology
  • Tuberculosis, Pleural* / blood
  • Tuberculosis, Pleural* / immunology
  • Tuberculosis, Pleural* / microbiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antibodies, Neutralizing
  • Antigens, Bacterial
  • Bacterial Proteins
  • Interleukin-2
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma