FELV-INDUCED ALTERATIONS OF FELINE HEMATOPOIETIC CELLS

猫白血病病毒的独特之处在于它能够引起 退化性（免疫抑制）或 肿瘤 FeLV免疫抑制综合征的发病机制显示出许多 与HTLV-III诱导的免疫缺陷疾病综合征相似 （艾滋病）在人类。 因此，获得了关于FeLV疾病光发生的见解 可以普遍适用于更好地了解艾滋病。 的关键 更好地了解FeLV的细胞和分子机制 诱导的疾病将是鉴定特定的T-、B-和单核细胞 细胞表面标记，这将允许识别，计数， 这些单眼亚群的分离和功能分析 FeLV疾病综合征。 该提案的主旨是发展 抗猫单核细胞表面抗原的单克隆抗体， 能够区分功能特异性表型。 现有分离 将采用Percoll和ConA-FACS等技术来富集 用作免疫原的推定表型和功能亚群 将进行单核细胞、TH、TS和淋巴细胞细胞毒性功能的测定。 用于筛选抗体产生克隆的亚群特异性。 这些抗体对单核细胞亚群的特异性将是 经FACS和抗体依赖性补体耗竭研究证实， 介导的细胞裂解或抗体淘选技术。 用抗体探针 和建立表型-功能关系的体外试验，我们 将遵循表型特征（流式细胞术）和单核细胞 实验感染KT和Rickard的猫PBL功能 FeLV菌株。 这将提供重要的信息， 在FeLV进展过程中的细胞群和功能中， 免疫抑制（KT株）和白血病（R株）综合征。 最后， 我们将使用抗体探针和荧光激活细胞分选 在治疗过程中跟踪FeLV感染的PBL细胞类型， 这些感染。 这不仅将提供有价值的信息， 用于猫的免疫生物学的未来研究的试剂，但将 提供FeLV疾病发病机制的重要信息。 以来 猫FeLV的发病机制与HTLV-III有许多相似之处， 人类艾滋病的病原体，这些研究将有助于我们 了解这一重要的人类疾病。

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.