Mechanisms of in vivo modulation of granulomatous inflammation in murine schistosomiasis japonicum.

Abstract

In schistosomiasis japonicum, the major pathologic lesion is the granulomatous inflammation that occurs around parasite eggs trapped in the liver. The size of these granulomas and their major sequela, a rise in portal pressure, both peak between 8 and 10 weeks after infection and then spontaneously decrease. We have shown that the adoptive transfer of the serum, but not lymphoid cells, of 30-week-infected mice caused decreases in both the size of the hepatic granulomas and the portal pressure of acutely infected recipient mice. The present study examines the role of both humoral (serum) and cellular immune mechanisms of modulation throughout the course of murine infection. Pools of serum (0.3 ml), spleen cells (5 X 10(7)), or splenic T cells (2 X 10(7)) from mice infected for 10, 20, and 30 weeks were adoptively transferred into mice at 4 and 5 weeks of infection. One week later (6 weeks postinfection), the portal pressure and size of hepatic granulomas in all recipient mice were determined. The 10-week-infected mouse serum occasionally lowered these values, but serum from 20- and 30-week-infected animals was consistently suppressive. The active component of 30-week-infected mouse serum coeluted with immunoglobulin G1. In contrast, 10-week-infected spleen cells or T cells consistently lowered portal pressure and granulomatous inflammation, but 20- and 30-week spleen cells did not. The phenotype of these suppressive T cells was Lyt-1-2+. These in vivo observations confirm earlier in vitro studies on cellular and humoral immune modulation of egg antigen-induced spleen cell blastogenesis. The current study demonstrates that both cellular and humoral regulation of granulomatous inflammation occur in murine schistosomiasis japonicum but with different kinetics: cellular mechanisms are maximal early (10 weeks) while humoral mechanisms predominate late during the chronic stage of infection (20 and 30 weeks).