title: Regulatory CD4+CD25+ T Cells Dampen Inflammatory Disease in Murine Mycoplasma Pneumonia and Promote IL-17 and IFN-γ Responses.
abstract: Mycoplasmas cause respiratory diseases characterized by persistent infection and chronic airway inflammation. Mycoplasma lung disease is immunopathologic, with CD4+ Th cells determining both disease severity and resistance to infection. Th2 cell responses promote immunopathology, while Th1 cells confer resistance to infection. However, regulatory CD4+ T cells may also have a role in the pathogenesis of mycoplasma respiratory diseases. We hypothesized Treg cells control the severity of the inflammatory lesions and may also promote persistence of infection. To examine this, BALB/c mice were depleted of CD25+ cells, and had increased disease severity due to Mycoplasma pulmonis infection. Increases in mycoplasma antibody responses and lymphocyte infiltration into lungs also occurred after CD25+ cell depletion. CD4+CD25+ regulatory T cells promoted IFN-γ and IL-17 mycoplasma-specific CD4+ T cell responses in vitro and in vivo, while dampening IL-13+ Th responses. Neither IL-10 nor TGF-ß expression was detected in CD4+CD25+ T cells from lymph nodes. Thus, a regulatory T cell population plays an important role in controlling damaging immune responses in mycoplasma respiratory disease but does not contribute to persistence of infection. It appears that a regulatory T cell population preferentially dampens Th2 cell-mediated inflammatory responses to mycoplasma through a mechanism independent of IL-10 or TGF-ß characteristic of "classic" Treg cells.
authors.affiliation: Preclinical Services and the Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, 76107, United States of America.
authors.forename: Adam N
authors.initials: AN
authors.lastname: Odeh
authors.affiliation: Preclinical Services and the Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, 76107, United States of America.
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Simecka
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008807:Mice, Inbred BALB C; D045803:Mycoplasma pulmonis / Q000502:physiology; D010641:Phenotype; D011019:Pneumonia, Mycoplasma / Q000097:blood / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma