IMMUNOREGULATORY IDIOTYPES STIMULATE T-HELPER-1 CYTOKINE RESPONSES INEXPERIMENTAL SCHISTOSOMA-MANSONI INFECTIONS

Inbred male CBA/J mice with chronic Schistosoma mansoni infections dev elop two distinct syndromes. Hypersplenomegaly syndrome (HSS) demonstr ates pathologic similarities to the hepatosplenic form of chronic huma n schistosomiasis, and moderate splenomegaly syndrome (MSS) resembles the asymptomatic intestinal form. Immunoaffinity-purified Abs against S. mansoni soluble egg Ags (SEA) from infected patients' sera differ i diotypically according to the donor's clinical form of the disease. We now show that immunoaffinity-purified anti-SEA Abs (Id) from MSS or H SS mice parallel idiotypic preparations of the analogous human clinica l form by their differential ability to stimulate the proliferation of anti-Id T cells. MSS Id preparations stimulate spleen cells from eith er MSS or HSS animals. In contrast, HSS Id does not stimulate spleen c ells from either group. In an anti-SEA ELISA, MSS and HSS Id preparati ons contained comparable levels of IgM and IgG1. However, the MSS Id p reparation had higher levels of SEA-specific IgG2a and IgG2b than did HSS Id. The Ig isotypes of these Id preparations suggested differences in cytokine expression patterns. Studies of the cytokine profiles of the spleen cells responding to anti-SEA Id preparations demonstrated t hat while Id preparations from acutely infected mice stimulate IL-4 an d IL-10 production, Id preparations from chronic MSS mice stimulate IF N-gamma production. HSS Id did not stimulate the production of any of these cytokines. The possibility that distinct immunoregulatory enviro nments may contribute to the development of MSS and HSS correlates wit h earlier hypotheses that hepatosplenic pathology results at least in part from a lack of development or expression of appropriate regulator y Ids.