CD4+ CD25+ transforming growth factor-beta-producing T cells are present in the lung in murine tuberculosis and may regulate the host inflammatory response.
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.
Mason
C M
CM
Pulmonary/Critical Care Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. mason@lsuhsc.edu
Porretta
E
E
Zhang
P
P
Nelson
S
S
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D007108:Immune Tolerance / Q000276:immunology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10