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 要么是退行性(免疫抑制)，要么是 肿瘤。FeLV免疫抑制综合征的发病机制有多种 与HTLV-III诱导的免疫缺陷病综合征的相似性 (艾滋病)在人类身上。因此，在FeLV疾病的光发生方面获得了见解 可能普遍适用于更好地了解艾滋病。至关重要的是 更好地理解FeLV的细胞和分子机制 诱发疾病将是对特定的T、B和单核细胞的鉴定 细胞表面标记，这将允许识别、计数、 猫这些单细胞亚群的分离和功能分析 伴随着FeLV病综合征。这项提议的主旨将是发展 抗猫单核细胞表面抗原的单抗 能够区分特定功能的表型。既有分离 Percoll和Con A-FACS等技术将用于丰富 用作免疫原的表型和功能亚群 单核细胞、TH、TS和淋巴细胞细胞毒功能的检测将是 用于筛选产生抗体的克隆的亚群特异性。 这些抗体对单个核亚群的特异性将是 经FACS和抗体依赖补体耗竭研究证实- 介导性细胞裂解或抗体淘洗技术。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)和单个核细胞 实验感染KT和立克次体猫的外周血淋巴细胞功能 FeLV毒株。这将提供有关更改的重要信息 在乙型病毒性肝炎进展过程中的细胞群和功能 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的细胞分选 观察慢性肝炎期间感染FeLV的PBL细胞的类型 这些感染。这不仅将提供有价值的信息和 未来对猫的免疫生物学研究的试剂，但将 为FeLV病的发病机制提供重要信息。自.以来 猫FeLV的发病机制与HTLV-III有许多相似之处， 人类艾滋病的致病因子，这些研究将有助于我们的 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.