HUMAN SCHISTOSOMIASIS-MANSONI - STUDIES ON IN-VITRO GRANULOMA MODULATION

Infection with Schistosoma mansoni induces humoral and T cell mediated responses and leads to a delayed hypersensitivity that results in gra nulomatous inflamatory disease around the parasite eggs. Regulation of these responses resulting in a reduction in this anti-egg inflamatory disease is apparently determined by idiotypic repertoires of the pati ent, associated with genetic background and multiple external factors. We have previously reported on idiotype/anti-idiotype-receptor intera ctions in clinical human schistosomiasis. These findings support a hyp othesis that anti-SEA cross-reactive idiotypes develop in some patient s during the course of a chronic infection and participate in regulati on of anti-SEA cellular immune responses. We repport here on experimen ts which extend those observations to the regulation of granulomatous hypersensitivity measured by an in vitro granuloma model T cells from chronic intestinal schistosomiasis patients were stimulated in vitro w ith anti-SEA idiotypes and assayed in an autologous in vitro granuloma assay for modulation of granuloma formation. These anti-SEA idiotype reactive T cells were capable of regulating autologous in vitro granul oma formation. Both CD4 and CD8 T cells could be activated to regulate granuloma formation. This regulatory activity, initiated with stimula tory anti-SEA idiotypic antibodies, was antigenically specific and was dependent on the presence of intact (F(ab')2 immunoglobulin molecules . The ability to elicit this regulatory activity appears to be dose de pendent and is more easily demonstrated in chronically infected intest inal patients or SEA sensitized individuals. These data support the hy pothesis that anti-SEA cross reactive idiotypes are important in regul ating granulomatous hypersensitivy in chronic intestinal schistosomias is patients and these cross-reactive idiotypes appear to play a major role in cell-cell interactions which result in the regulation of anti- SEA cellular immune responses.