LOCALIZATION AND REGULATION OF IFN-GAMMA PRODUCTION WITHIN THE GRANULOMAS OF MURINE SCHISTOSOMIASIS IN IL-4-DEFICIENT AND CONTROL MICE

Schistosome granulomas from normal or IL-4-deficient C57BL/6 mice make little IFN-gamma and show no Th1 polarization. This could signify tha t these granulomas have few cells capable of IFN-gamma synthesis or th at such cells are under tight control, Granulomas can make IL-10 and T GF-beta, which can regulate IFN-gamma synthesis. Using FAGS analysis a nd ELISA, we explored the origin and regulation of IFN-gamma in schist osome granulomas from both IL-4(-/-) and IL-4(+/+) mice. FAGS analysis of intracytoplasmic IFN-gamma staining showed that some granuloma Thy 1.2(+) T cells (CD8(+) and CD4(+)) express IFN-gamma. Granulomas had N K1.1(+) cells, but they appeared to produce little or no IFN-gamma. Pu rified granuloma Thy1.2(+) cells made IFN-gamma in vitro, whereas isol ated NK1.1(+) lymphocytes secreted little even with rIL-12 stimulation . Culture of granuloma cells with blocking anti-IL-10 or anti-TGF-beta mAb or with rIL-12 substantially increased T cell IFN-gamma synthesis , particularly in the IL-4(-/-) animals. Cultured granuloma cells depl eted of Thy1.2(+) lymphocytes by Ab and C released no IFN-gamma, It is concluded that granuloma IFN-gamma comes from T cells, not NK cells. Also, this T cell-derived IFN-gamma is subject to IL-10 and TGF-beta r egulation, which is particularly evident in IL-4(-/-) mice, Thus, the Th2 granuloma of schistosomiasis has large numbers of activated Th1 or Th0 lymphocytes that are under tight restraint.