CD4(+) CD25(high) forkhead box protein 3(+) regulatory T lymphocytes suppress interferon-γ and CD107 expression in CD4(+) and CD8(+) T cells from tuberculous pleural effusions

Clin Exp Immunol. 2014 Feb;175(2):235-45. doi: 10.1111/cei.12227.

Abstract

Tuberculous pleural effusion is characterized by a T helper type 1 (Th1) profile, but an excessive Th1 response may also cause tissue damage that might be controlled by regulatory mechanisms. In the current study we investigated the role of regulatory T cells (Treg ) in the modulation of Th1 responses in patients with tuberculous (TB) pleurisy. Using flow cytometry we evaluated the proportion of Treg (CD4(+) CD25(high) forkhead box protein 3(+) ), interferon (IFN)-γ and interleukin (IL)-10 expression and CD107 degranulation in peripheral blood (PB) and pleural fluid (PF) from patients with TB pleurisy. We demonstrated that the proportion of CD4(+) CD25(+) , CD4(+) CD25(high) FoxP3(+) and CD8(+) CD25(+) cells were increased in PF compared to PB samples. Mycobacterium tuberculosis stimulation increased the proportion of CD4(+) CD25(low/neg) IL-10(+) in PB and CD4(+) CD25(low/neg) IFN-γ(+) in PF; meanwhile, CD25(high) mainly expressed IL-10 in both compartments. A high proportion of CD4(+) CD107(+) and CD8(+) CD107(+) cells was observed in PF. Treg depletion enhanced the in-vitro M. tuberculosis-induced IFN-γ and CD4(+) and CD8(+) degranulation responses and decreased CD4(+) IL-10(+) cells in PF. Our results demonstrated that in TB pleurisy Treg cells effectively inhibit not only IFN-γ expression but also the ability of CD4(+) and CD8(+) cells to degranulate in response to M. tuberculosis.

Keywords: CD107; T regulatory; pleural effusions; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Degranulation / immunology*
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Interferon-gamma / immunology*
  • Interleukin-10 / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Lysosomal-Associated Membrane Protein 1 / immunology*
  • Male
  • Mycobacterium tuberculosis / immunology
  • Pleural Effusion / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Tuberculosis, Pleural / immunology*
  • Young Adult

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL10 protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Lysosomal-Associated Membrane Protein 1
  • Interleukin-10
  • Interferon-gamma