Immunoregulatory idiotypes stimulate T helper 1 cytokine responses in experimental Schistosoma mansoni infections
Montesano, M.A.; Freeman, G.L.; Secor, W.E.; Colley, D.G.
Journal of Immunology 158(8): 3800-3804
1997
ISSN/ISBN: 0022-1767 PMID: 9103446 Document Number: 477255
Inbred male CBA/J mice with chronic Schistosoma mansoni infections develop 2 distinct syndromes: hypersplenomegaly syndrome (HSS) which demonstrates pathological similarities to the hepatosplenic form of chronic human schistosomiasis, and moderate splenomegaly syndrome (MSS) which resembles the asymptomatic intestinal form of the disease. Immunoaffinity-purified antibodies against S. mansoni soluble egg antigens (SEA) from sera of infected patients differ idiotypically according to the clinical form of the disease. It was shown that immunoaffinity-purified anti-SEA antibodies (Id) from MSS or HSS mice paralleled idiotypic preparations of the analogous human clinical form by their differential ability to stimulate the proliferation of anti-Id T cells. MSS Id preparations stimulated spleen cells from either MSS or HSS mice. In contrast, HSS Id did not stimulate spleen cells from either group. In an anti-SEA ELISA, MSS and HSS Id preparations contained comparable levels of IgM and IgG1. However, the MSS Id preparation had higher levels of SEA-specific IgG2a and IgG2b than 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 that while Id preparations from acutely infected mice stimulated interleukin (IL)-4 and IL-10 production, Id preparations from chronic MSS mice stimulated interferon- gamma production. HSS Id did not stimulate the production of any of these cytokines. The possibility that distinct immunoregulatory environments may contribute to the development of MSS and HSS correlates with earlier hypotheses that hepatosplenic pathology results at least in part from a lack of development or expression of appropriate regulatory Ids.