Suppression of immunopathology in schistosomiasis by antigen-daunomycin immunoconjugate I-In vitro studies on antigen specificity and genetic restriction

ABSTRACT

Soluble Egg Antigen [SEA], is the major stimulus for immunopathological lesions [granuloma formation and fibrosis] in schistosomiasis. Antigen presenting cells and T-Iymphocytes with receptors for SEA are primarily responsible for the induction and regulation of the immunopathology through the production of cytokines. During the present work SEA was conjugated to Daunomycin [DM], a cytotoxic antibiotic of the rhodomycin group. Antigen presenting cells and T -lymphocytes bearing surface receptors for SEA bind, internalize and activate the DM. Activated DM, inhibits RNA and DNA synthesis leading to inactivation and/or death of the targeted cells. The suppression effects of the Antigen-Daunomycin [Ag-DM] were assessed in vitro. Ag-DM conjugates demonstrated significant suppression of multiple in vitro parameters that depend on cellular reactivity to a specific antigen. The parameters were Antigen Mediated Blast Transformation [AMBT], In Vitro Granuloma Formation [IVGF] and cytokine production. The Suppression was a dose dependent and antigen specific, but not genetically restricted. DM alone demonstrated severe non-specific cytotoxicity. The studies support the feasibility of using antigen specific cytotoxic immunoconjugates to limit the pathological lesions in schistosomiasis