Failure of immunosuppressive mechanisms in human Schistosoma mansoni infection with hepatosplenomegaly.

The basis for development of hepatosplenic disease and attendant morbidity in Schistosoma mansoni-infected individuals is uncertain but may relate to defective modulation of immunopathology. Individuals 14 to 30 years of age from a village in the Nile Delta in Egypt were selected for study: 32 were infected with S. mansoni but lacked hepatosplenomegaly (mean fecal egg excretion +/- standard error of the mean, 1,142 +/- 79 eggs per g), 9 had S. mansoni infection and hepatosplenomegaly (1,267 +/- 197 eggs per g), and 12 were uninfected. The ratio of OKT4 helper/OKT8 suppressor cells in peripheral blood mononuclear cells was reduced in infected subjects without hepatosplenomegaly to 1.4 +/- 0.1 compared with a ratio of 1.7 +/- 0.1 (P less than 0.05) in uninfected subjects. In contrast, this ratio was increased in the group with hepatosplenomegaly to 2.7 +/- 0.3 (P less than 0.01). Schistosome antigen-induced [3H]thymidine incorporation in peripheral blood mononuclear cells was comparable in infected subjects without (5,837 +/- 1,009 cpm) and with (3,329 +/- 738 cpm; P greater than 0.1) hepatosplenomegaly. Depletion of adherent suppressor cells significantly increased the responses in the group lacking organomegaly (14,028 +/- 1,683 cpm; P less than 0.001) but not in the hepatosplenomegaly group (5,046 +/- 1,830 cpm; P greater than 0.5); this difference in response of nonadherent cells to soluble worm antigenic preparation was statistically significant (P less than 0.02) and not explained by quantitative shifts in OKT8 suppressor cells. Thus, in S. mansoni infection, subjects with hepatosplenomegaly are distinctive in their lack of an immunosuppressive balance of T-lymphocyte subpopulations and in the absence of functional adherent suppressor cells. Defective immunoregulatory mechanisms could be important in the genesis of hepatosplenic disease and its morbid sequelae.