CD4+ CD25+ transforming growth factor-beta-producing T cells are present in the lung in murine tuberculosis and may regulate the host inflammatory response
| Autor: | Elizabeth Porretta, Steve Nelson, Ping Zhang, Carol M. Mason |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
CD4-Positive T-Lymphocytes
Regulatory T cell medicine.medical_treatment Immunology Interleukin 21 Mice Basic Immunology Interferon T-Lymphocyte Subsets Transforming Growth Factor beta medicine Immune Tolerance Immunology and Allergy Animals IL-2 receptor Lung Tuberculosis Pulmonary Cells Cultured Mice Inbred BALB C biology Interleukin-2 Receptor alpha Subunit T lymphocyte Interleukin-10 Interleukin 10 medicine.anatomical_structure Cytokine biology.protein Cytokines Antibody medicine.drug |
| Zdroj: | Clinical and experimental immunology. 148(3) |
| ISSN: | 0009-9104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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