CD4+ CD25+ transforming growth factor-beta-producing T cells are present in the lung in murine tuberculosis and may regulate the host inflammatory response

Clin Exp Immunol. 2007 Jun;148(3):537-45. doi: 10.1111/j.1365-2249.2007.03371.x. Epub 2007 Mar 16.


CD4(+) CD25(+) regulatory T cells produce the anti-inflammatory cytokines transforming growth factor (TGF)-beta or interleukin (IL)-10. Regulatory T cells have been recognized to suppress autoimmunity and promote self-tolerance. These cells may also facilitate pathogen persistence by down-regulating the host defence response during infection with Mycobacterium tuberculosis. We evaluated TGF-beta(+) and IL-10(+) lung CD4(+) CD25(+) T cells in a murine model of M. tuberculosis. BALB/c mice were infected with approximately 50 colony-forming units of M. tuberculosis H37Rv intratracheally. At serial times post-infection, lung cells were analysed for surface marker expression (CD3, CD4, CD25) and intracellular IL-10, TGF-beta, and interferon (IFN)-gamma production (following stimulation in vitro with anti-CD3 and anti-CD28 antibodies). CD4(+) lung lymphocytes were also selected positively after lung digestion, and stimulated in vitro for 48 h with anti-CD3 and anti-CD28 antibodies in the absence and presence of anti-TGF-beta antibody, anti-IL-10 antibody or rmTGF-beta soluble receptor II/human Fc chimera (TGFbetasrII). Supernatants were assayed for elicited IFN-gamma and IL-2. Fluorescence activated cell sorter analyses showed that TGF-beta- and IL-10-producing CD4(+) CD25(+) T cells are present in the lungs of infected mice. Neutralization of TGF-beta and IL-10 each resulted in increases in elicited IFN-gamma, with the greatest effect seen when TGFbetasrII was used. Elicited IL-2 was not affected significantly by TGF-beta neutralization. These results confirm the presence of CD4(+) CD25(+) TGF-beta(+) T cells in murine pulmonary tuberculosis, and support the possibility that TGF-beta may contribute to down-regulation of the host response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Immune Tolerance / immunology
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / immunology
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Lung / immunology
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocyte Subsets / immunology*
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / biosynthesis*
  • Tuberculosis, Pulmonary / immunology*


  • Cytokines
  • Interleukin-2 Receptor alpha Subunit
  • Transforming Growth Factor beta
  • Interleukin-10