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: 3796555
• 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/3796555
• 关键词: T lymphocyte; antigen presenting cell; blood /lymphatic neoplasm; bone marrow transplantation; cell population study; histocompatibility antigens; homologous transplantation; human tissue; 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 repopu-lation 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 in part to a lack of murine antigen presenting cell activation.

从骨髓中消除T细胞在同种异体移植中都是令人感兴趣的。 自体骨髓移植--作为一种防止移植物 同种异体骨髓移植中的抗宿主病 消除或清除表达T细胞表面的恶性细胞 自体骨髓治疗T细胞肿瘤的骨髓标志物 移植 我们开发了一种方法， 恶性T细胞骨髓群体的骨髓;这些方法是 然后用于临床方案，评估使用 同种异体HLA错配、T细胞耗竭骨髓和自体骨髓 清除恶性T细胞治疗侵袭性 造血系统恶性肿瘤 恒河猴临床前研究 证明了CD 4 + T细胞重建和体内T细胞的发育， 细胞免疫活性与输注的T细胞数量相关， 骨髓中的残留T细胞可能是 细胞耗尽的骨髓在骨髓的产生中发挥了核心作用。 随后的T细胞群。 这一结论得到了证实， 小鼠研究中，三个T细胞祖细胞库已被 确定了有助于最终T细胞再增殖的 骨髓移植 这些再生T细胞的功能能力 细胞群也是令人感兴趣的。 人类T辅助细胞反应 通过刺激鼠细胞表达的异种MHC编码抗原 研究发现，在人类中， 人T辅助细胞功能的评估， 需要对刺激性鼠抗原进行再加工， 与人类II类基因产物相关。 的要求 鼠抗原的再加工和应答型细胞的呈递 （而不是小鼠刺激细胞）被发现部分是由于 缺乏鼠抗原呈递细胞活化。