FELV-INDUCED ALTERATIONS OF FELINE HEMATOPOIETIC CELLS

点击翻译按钮获取中文摘要

Feline leukemia virus is unique in that it is capable of causing hematopoietic diseases that are either degenerative (immunosuppressive) or neoplastic. The pathogenesis of FeLV immunosuppression syndrome shows many similarities to that of HTLV-III-induced immunodeficiency disease syndrome (AIDS) in humans. Thus, insights gained on the photogenesis of FeLV disease may be generally applicable to a better understanding of AIDS. Critical to better understanding of the cellular and molecular mechanisms of FeLV induced diseases will be the identification of specific T-, B-, and monocyte cell-surface markers, which will permit the identification, enumeration, separation and functional analysis of these monoclear subpopulations in cats with FeLV disease syndromes. The thrust of this proposal will be to develop monoclonal antibodies to feline mononuclear cell surface antigens that are capable of discriminating function-specific phenotypes. Existing separation techniques such as Percoll and Con A-FACS will be employed to enrich for putative phenotypic and functional subpopulations to be used as immunogens Assays for monocyte, TH, TS and lymphocyte cytotoxic functions will be employed to screen antibody-producing clones for subpopulation specificity. Specificity of these antibodies for mononuclear subpopulations will be confirmed by FACS and depletion studies with antibody-dependent complement- mediated cell lysis or antibody panning techniques. With antibody probes and in vitro assays for establishing phenotype-function relationships, we will follow phenotype profiles (flow cytometry) and mononuclear cell functions of PBL of cats experimentally infected with the KT or Rickard strain of FeLV. This will provide important information on the alterations in cell populations and functions during the progression of FeLV in immunosuppression (KT strain) and leukemia (R strain) syndromes. Finally, we will employ the antibody probes and fluorescence activated cell sorting to follow the types of PBL cells infected with FeLV during the course of these infections. This will not only provide valuable information and reagents for future studies on the immunobiology of the cat, but will provide important information on the pathogenesis of FeLV diseases. Since the pathogenesis of FeLV in cats has many similarities to HTLV-III, the causative agents of AIDS in humans, these studies will contribute to our understanding of this important human disease.