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.

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Mycoplasmas cause respiratory diseases characterized by persistent infection and chronic airway inflammation. Mycoplasma lung disease is immunopathologic, with Th cells determining disease severity and resistance to infection. Th2 cell responses promote immunopathology; Th1 cells confer resistance to infection. However, little is known about the role of Treg cells in mycoplasma respiratory diseases. We hypothesized Treg cells control the severity of the inflammatory lesions and may also promote persistence of infection, as found in other diseases. To examine this, mice, given anti-CD25 antibody to deplete Treg cells, had increased disease severity due to Mycoplasma pulmonis infection. There was however no affect on mycoplasma numbers recovered from the lungs. Treg cells promote the secretion of IFN-γ and IL-17 mycoplasma-specific CD4+ T cell responses in vitro. We were unable to detect significant changes in IL-10 and TGF-β production. In addition, Treg cell depletion increased Th2 (IL-13) responses. Populations of Treg cells from lymph nodes had increased expression of IFN-γ or IL-17 after infection. Thus, Treg cells play an important role in controlling damaging immune responses in mycoplasma respiratory infection but do not influence the level of mycoplasma infection. It appears that Treg cells dampen mycoplama inflammatory disease through a novel mechanism mediated production of IFN-γ and IL-17.