PATHOLOGY AND PATHOGENESIS OF T-CELL LOSS IN HVG DISEASE

本实验室的工作旨在了解 同种异体HVG综合征的发病机制， 可能在围产期接种半同种异体淋巴造血细胞后 细胞转化为易感的近交系小鼠。 已完成的工作表明 这种疾病的主要病理特征是T细胞减少，B 细胞增生和免疫复合物形成。 该提案的具体目标包括： 1.为了确定标记的F1杂合T细胞在它们的免疫后的作用和命运， 接种到RFM宿主中。 2.为了鉴定RFM围产期脾脏中存在的细胞， 识别并对抗供体F1细胞，重点是T和NK细胞。 3.研究F1供体和宿主T细胞丢失的机制 在HVG反应期间，以及是否存在 T细胞亚群在同种异体反应期间丢失， 与观察到的显著血清变化相关。 组织学、细胞学、细胞遗传学和体外培养技术 将用于 成功地完成这项工作应该会产生重要的信息 直接适用于临床骨髓移植的机制 排斥反应、急性和慢性移植物抗宿主综合征、耐受性和 有利于肾病免疫复合物形成的细胞变化。

Work in this laboratory has been directed toward the understanding of the pathogenesis of allogenic HVG syndrome, a disease of altered immunity which may follow the perinatal inoculation of semiallogenic lymphohemopoietic cells into susceptible strains of inbred mice. Work completed has shown that the main pathologic features of the disease are T cell depletion, B cell hyperplasia and immune complex formation. The specific aims of the proposal include: 1. To ascertain the role and fate of labelled F1 hybrid T cells after their inoculation into RFM hosts. 2. To identify the cells present in the spleens of RFM perinates which can recognize and react against donor F1 cells, with emphasis on T and NK cells. 3. To study the mechanism(s) by which F1 donor and host T cells are lost during the HVG reaction, and whether there is a differential sensitivity of T cell subsets to loss during the allogenic reaction which can be correlated with the marked serum changes observed. Histopathologic, cytologic, cytogenetic and in vitro culture techniques will be used. Successful completion of the work should yield important information directly applicable to the mechanisms of clinical bone marrow graft rejection, acute and chronic Graft Versus Host syndromes, tolerance and the cellular changes which favor the formation of nephropathic immune complexes.