Feline leukemia viral infected cats are a unique model to study immunosuppression, acquired immunodeficiency syndrome and immune mechanism(s) involved in the initiation and progression of neoplastic growth. In this proposal we plan to take advantage of the dramatic unequivocal reductions of tumor size, changes in marrow and peripheral blood, neoplastic cell populations and clearance of viremia following treatment of virus infected and/or malignant cells with SpA therapy (ex vivo immunoadsorption or injection). We will treat additional animals to determine whether the responses are biostatistically significant. We will examine both humoral (Complement (C) and C activation products) and cell mediated immunity. We will first identify T cell subsets which are poorly defined in the cat. Monoclonal antibodies (Mabs) to kitten thymocytes have been initiated and we have established for the feline system a reverse plaque hemolytic assay for evaluating B cells and roles of T helper or suppressor on induction of Ig synthesis. We now have a Mab which identifies T-S cells. A major goal is to mimic in vitro immunosuppressive FeLV effects observed in vivo i.e. to study the effects on non infectious FeLV and its purified components on T cell functions. We have already shown that U.V. FeLV has a direct suppressive effect feline IFN production and IgG secretion in vitro. Furthermore p15E peptide homologous to retroviral envelope proteins has a dramatic suppressive effect on polyclonal B cell activation by Staphylococcus Protein A. If we can show immunomodulatory influences of retrovirus and its peptides on animal or human cells, not only will we obtain a greater understanding of the in vivo potent immunosuppressive effects of retroviruses, particularly in acquired immunodeficiency syndrome, but also the immunoregulatory role of viruses may become sources of powerful pharmacologic agents.
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