Interferon-γ antagonizes transforming growth factor-β2-mediated immunosuppression in murine Toxoplasma encephalitis

The in vivo modulating activity of recombinant transforming growth factor (TGF)-beta(2) on acute toxoplasmosis was evaluated in both Toxoplasma gondii susceptible C57BL/6 and resistant BALB/c mice. TGF-beta(2) lethally exacerbated Toxoplasma encephalitis in C57BL/6, but not in BALB/c mice. In C57BL/6 mice, TGF-beta(2) induced a profound dose-dependent increase of the intracerebral parasitic load as well as a reduction of IFN-gamma levels in serum and cerebrospinal fluid with a coincident decrease of MHC class II antigen expression of macrophages, microglial cells. and B cells. Furthermore, TGF-beta(2)-treated C57BL/6 mice showed a reduced activation of CD4(+) and CD8(+) T cells and a diminished recruitment of immune cells to the brain. The TGF-beta(2)-mediated development of lethal toxoplasmosis in C57BL/6 mice was abolished by treatment with recombinant interferon (IFN)-gamma. (C) 1998 Elsevier Science B.V.