T CELL RESPONSES IN BONE MARROW TRANSPLANTATION

T 细胞在骨髓移植中的反应

• 批准号: 3813478
• 负责人: R E GRESS
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3813478
• 关键词: CD4 molecule; Macaca mulatta; T lymphocyte; antigen presenting cell; autologous transplantation; bone marrow transplantation; cell population study; helper T lymphocyte; histocompatibility; histocompatibility antigens; human tissue; laboratory mouse; leukocyte activation /transformation; major histocompatibility complex; organ culture

Concerns that a functionally effective T cell repertoire might never develop in the setting of MHC-mismatched marrow transplantation are based on defective T cell responses in vivo observed in murine bone marrow chimeras constructed between MHC disparate strains. The incompetence is not due to inherent T cell defects, but rather to the restriction specificities of the T cells such that those MHC determinants recognized as self (host type) are not expressed by the antigen presenting cells which are of donor type. The T cell response to antigen is therefore defective. To evaluate whether T cell maturation is comparable in mouse and man, the development of T cell responses in a primate, the rhesus monkey, has been studied. The biology of T cell recovery has first been investigated in animals following T cell depleted autologous marrow transplantation. The time course of CD4+ T cell reconstitution and the time course of the development of in vivo T cell immunocompetence as defined by the ability to respond to an organ allograft correlated with the number of T cells infused in the marrow, and did not correlate with marrow cell dose or with time of hematopoietic reconstitution, raising the possibility that residual T cells in the infused T cell depleted marrow played a central role in the generation of subsequent T cell populations. This would imply that the generation of T cells in marrow grafted primates may not be the same as in the mouse.

担心功能上有效的T细胞谱系可能永远不会 在MHC不匹配骨髓移植的背景下发展是基于 小鼠骨髓中观察到的体内缺陷T细胞反应 构建在MHC不同菌株之间的嵌合体。无能之处在于 不是由于先天T细胞缺陷，而是由于限制 T细胞的特异性，使得这些MHC决定因素被识别为 自身(宿主类型)不是由抗原提呈细胞表达的， 都是捐赠型的。因此T细胞对抗原的反应是有缺陷的。 为了评估小鼠和人的T细胞成熟度是否相当， 在灵长类动物恒河猴中，T细胞反应的发展已经被 学习。T细胞恢复的生物学研究首次在#年进行。 T细胞耗尽的自体骨髓移植动物。这个 CD_4~+T细胞重建的时程和T细胞的时程 体内T细胞免疫活性的发展由以下能力定义 对器官移植的反应与输入的T细胞的数量相关 在骨髓中，与骨髓细胞剂量或时间无关。 造血重建，增加了残留T细胞 在输注的T细胞中，耗尽的骨髓在 后续T细胞群的生成。这将意味着 在移植骨髓的灵长类动物中，T细胞的生成可能与 那只老鼠。