Feline leukemia pathogenesis presents a well characterized model of retrovirus-mediated disease resulting in either a progressive chronic viremia with immune suppression and malignancy or a regressive disease without apparent retroviral damage. Factors other than virus inoculum, strain and age related susceptibility which lead to viral persistence in the host are obscure. In this multifaceted study, we propose to examine the critical immunological and nonspecific events which predispose the host to disease progression.
The specific aims are: to examine the role of cell membrane FeLV-induced changes on cell function and cell-cell recognition interactions necessary for developing adequate host protection; to compare the immune response in progressor and regressor cats by studying phagocytic and intracellular killing mechanisms, production of immune modulators such as interferon and prostaglandins, and examining the role of immune complex formation on pathogenesis and immunomodulation; and last to ascertain whether transient or latent undetectable FeLV infection in cats produces long term hemolymphatic defects which may become evident during subsequent concomitant disease or immunosuppressive drug treatment. Methods for studying these parameters include: Percoll separation of hemolymphatic cells; antibody-ELISA on cells for identification or retroviral-induced cell membrane changes; cell affinity chromatographic separation of altered cells for functional studies; detection of Ia-like antigen expression and subsequent changes after infection by use of the feline MLR; titration of prostaglandin production and cellular levels of cAMP and cGMP by RIA; C1q ELISA assay for detection of circulating immune complexes; and the use of Staph Protein A columns for isolation of CIC for analysis and in vitro cell function assay, lymphocyte blast transformation and phagocytosis assays.
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