Regulatory CD4.sup.+CD25.sup.+ T Cells Dampen Inflammatory Disease in Murine Mycoplasma Pneumonia and Promote IL-17 and IFN-[gamma] Responses

Mycoplasmas cause respiratory diseases characterized by persistent infection and chronic airway inflammation. Mycoplasma lung disease is immunopathologic, with CD4.sup.+ 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.sup.+ 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.sup.+ 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.sup.+ cell depletion. CD4.sup.+ CD25.sup.+ regulatory T cells promoted IFN-[gamma] and IL-17 mycoplasma-specific CD4.sup.+ T cell responses in vitro and in vivo, while dampening IL-13.sup.+ Th responses. Neither IL-10 nor TGF-ß expression was detected in CD4.sup.+ CD25.sup.+ 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.