T CELL FUNCTION IN T CELL DEPLETED BONE MARROW TRANSPLANTATION

T 细胞耗竭骨髓移植中的 T 细胞功能

• 批准号: 3774401
• 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/3774401
• 关键词: Macaca mulatta; T lymphocyte; antigen presentation; antigen presenting cell; autologous transplantation; blood /lymphatic neoplasm; bone marrow purging; bone marrow transplantation; cell population study; helper T lymphocyte; histocompatibility antigens; homologous transplantation; laboratory mouse; leukocyte activation /transformation; major histocompatibility complex

The elimination of T cells from marrow is of interest both in allogeneic and autologous marrow transplantation - - as a means of preventing graft versus host disease in allogeneic marrow transplantation and as a means of eliminating or purging malignant cells expressing T cell surface markers from marrow in treating T cell neoplasms by autologous marrow transplantation. We developed approaches for depleting normal and malignant T cell marrow populations from marrow; these approaches were then used in clinical protocols assessing the feasibility of utilizing allogenic HLA-mismatched, T cell depleted marrow and autologous marrow purged of malignant T cells in the treatment of aggressive hematolymphopoietic malignancies. Preclinical studies in rhesus monkeys demonstrated that CD4+ T cell reconstitution and development of in vivo T cell immunocompetence correlated with the number of T cells infused in the marrow 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 conclusion has been confirmed in murine studies in which three T cell progenitor pools have been identified which contribute to final T cell repopulation following marrow transplantation. The functional capacities of these regenerated T cell populations is also of interest. The human T helper cell response to xenogenic MHC encoded antigens expressed by stimulating murine cell populations has been studied and found to be of special use in the assessment of human T helper cell function in that this primary response requires reprocessing of the stimulating murine antigens and presention in association with human Class II gene products. The requirement for reprocessing of murine antigen and presentation by responder-type cells (rather than murine stimulating cells) was found to be due to a lack both of murine antigen presenting cell activation and responder T cell activation.

从骨髓中清除T细胞在同种异体移植中都是有意义的 和自体骨髓移植--作为预防移植的一种手段 在异基因骨髓移植中对抗宿主疾病和作为一种手段 清除或清除表达T细胞表面标志的恶性细胞 自体骨髓在T细胞肿瘤治疗中的应用 移植。我们开发了耗尽正常和 来自骨髓的恶性T细胞骨髓群体；这些方法是 然后用于临床方案评估使用的可行性 同种异体人类白细胞抗原不匹配、T细胞耗尽的骨髓和自体骨髓 恶性T细胞清除在侵袭性疾病治疗中的应用 血液淋巴系统恶性肿瘤。恒河猴的临床前研究 研究表明，体内CD4+T细胞的重建和发育 细胞免疫活性与输注的T细胞数量相关 骨髓增加了输注T细胞中残留T细胞的可能性 细胞耗尽的骨髓在随后的骨髓生成中起着核心作用 T细胞群。这一结论已在小鼠研究中得到证实。 其中已经确定了三个T细胞祖细胞池， 有助于骨髓移植后T细胞的最终再繁殖。 这些再生T细胞群的功能能力也是 感兴趣的人。人类辅助性T细胞对异种MHC编码的应答 通过刺激小鼠细胞群表达的抗原已经被研究 并被发现在评估人类T辅助细胞方面有特殊用途 函数，因为此主响应需要重新处理 与人类类相关的刺激性小鼠抗原和存在 二是基因产品。对小鼠抗原再加工的要求和 由响应型细胞(而不是小鼠刺激)呈现 细胞)被发现是由于缺乏小鼠抗原提呈 细胞激活和应答T细胞激活。