SUPPRESSION OF IMMUNOPATHOLOGY IN SCHISTOSOMIASIS BY INTERLEUKIN-2-TARGETED FUSION TOXIN, DAB(389)IL-2 .1. STUDIES OF IN-VITRO AND IN-VIVO EFFICACY

Schistosomiasis causes pathology in an estimated 200 million individua ls, Clinical disease is caused by a complex immunopathologic response to the parasite ova, which are deposited in the host tissues, This imm unopathologic response is caused by T lymphocytes which express the hi gh-affinity IL-2 receptor (IL-2R). DAB(389)IL-2 is a diphtheria toxin- IL-2 fusion toxin protein which functionally inactivates or kills cell s which bear the high-affinity IL-2R. DAB(389)IL-2 has been used in ma n to suppress IL-2R-dependent immune reactivity,Therefore, we reasoned that DAB(389)IL-2 might suppress immunopathology in schistosomiasis, In these studies we assessed the in vitro and in vive effects of DAB(3 89)IL-2 on the development of immunopathology in murine schistosomiasi s. DAB(389)IL-2 suppressed IL-2, lectin mitogen (Con A), and soluble S chistosoma mansoni egg antigen-induced lymphocyte proliferation and in vitro granuloma formation, In addition, DA-B(389)IL-2 suppressed in v itro IL-BR expression, DAB(389)IL-2 also suppressed the development of granulomas and collagen deposition in vive in the livers of infected animals. Therefore, DAB(389)IL-2 may have potential for the targeted r eduction of immunopathology due to schistosomiasis in man. (C) 1995 Ac ademic Press, Inc.