The pathogenesis of most human aplastic anemias is obscure due to difficulty in recognition and study of the early stages of the syndrome. The long-term objective of this study is to use the naturally occurring and experimentally reproducible model of feline erythroid aplasia to investigate the mechanisms of virus-induced aplastic anemia. Feline erythroid aplasia can be induced with the Kawakami-Theilen isolate of feline leukemia virus, a horizontally transmitted retrovirus. The model facilitates propective studies of the relationship between viral proteins, virus-specified cell surface neoantigens, humoral and cellular responses, and suppression of erythropoiesis.
The specific aims are to: determine if erythroid aplasia is mediated by viral damage to erythroid progenitors or to bone marrow accessory cells which regulate the differentiation and proliferation of erythroid progenitors; determine if viral expression by hemopoietic progenitors triggers immunologic elimination of the cells; determine if viral immune complexes suppress proliferation of erythroid progenitors; determine if latent FeLV infection predisposes to erythroid aplasia; and, determine if feline erythroid aplasia is an effective model for evaluating the effects of anti-thymocyte globulin therapy in aplastic anemia. Methods will include: culture and characterization of serial bone marrow samples in semi-solid medium for erythroid and granulocyte/macrophage progenitors, co-culture of subsets of bone marrrow mononuclear cells from normal cats and virus-positive cats, exposure of bone marrow cells to FELV or FeLV proteins, ex vivo immunosorption of IgG-complexes, anti-thymocyte globulin therapy, fractionation and extraction of viral proteins, cytotoxicity tests, and immunosuppression of cats with regressive infections to reactivate latent virus.
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