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 was 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 <0.05) in uninfected subjects. In contrast, this ratio was increased in the group with hepatosplenomegaly to 2.7 ± 0.3 (P <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 > 0.1) hepatosplenomegaly. Depletion of adherent suppressor cells significantly increased the responses in the group lacking organomegaly (14,028 ± 1,683 cpm; P <0.001) but not in the hepatosplenomegaly group (5,046 ± 1,830 cpm; P > 0.5); this differece in response of nonadherent cells to soluble worm antigenic preparation was statistically significant (P <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.