INTERFERON-GAMMA ANTAGONIZES TRANSFORMING GROWTH FACTOR-BETA(2)-MEDIATED IMMUNOSUPPRESSION IN MURINE TOXOPLASMA-ENCEPHALITIS

The in vivo modulating activity of recombinant transforming growth fac tor (TGF)-beta(2) on acute toxoplasmosis was evaluated in both Toxopla sma gondii susceptible C57BL/6 and resistant BALB/c mice. TGF-beta(2) lethally exacerbated Toxoplasma encephalitis in C57BL/6, but not in BA LB/c mice. In C57BL/6 mice, TGF-beta(2) induced a profound dose-depend ent increase of the intracerebral parasitic load as well as a reductio n of IFN-gamma levels in serum and cerebrospinal fluid with a coincide nt decrease of MHC class II antigen expression of macrophages, microgl ial cells. and B cells. Furthermore, TGF-beta(2)-treated C57BL/6 mice showed a reduced activation of CD4(+) and CD8(+) T cells and a diminis hed 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 S cience B.V.