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T CELL FUNCTION IN T CELL DEPLETED BONE MARROW TRANSPLANTATION

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:
3808609
负责人:
R E GRESS
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至

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中文摘要
翻译
从骨髓中清除表达T细胞表面的细胞 标记物在异体骨髓和自体骨髓中都很有价值 移植--作为预防移植物抗宿主病的一种手段 异基因骨髓移植和作为一种消除或 从骨髓中清除表达T细胞表面标志的恶性细胞 自体骨髓移植治疗T细胞肿瘤 开发了耗尽正常和恶性T细胞的方法 用淘洗和衍生单克隆法获得骨髓群体 针对T细胞特有的细胞表面分子的抗体。这些 方法被用来制定临床方案来评估 利用同种异体人类白细胞抗原不匹配、T细胞耗尽的可行性 同种异体骨髓和自体骨髓清除恶性T细胞 侵袭性血液淋巴系统恶性肿瘤的治疗。 对恒河猴的临床前研究表明,功能性T细胞 在接受T细胞耗尽的自体移植的动物中产生种群 骨髓。CD_4~+T细胞重建与慢性粒细胞白血病发生发展的时程 体内T细胞免疫活性与T细胞数量的关系 在骨髓中输注,与骨髓细胞剂量或 造血重建,增加了残留T细胞的可能性 输注的T细胞耗尽的骨髓中的细胞在 后续T细胞群的生成。它们的作用机制 输注的成熟T细胞产生可重组的外周T细胞 目前正在对小鼠模型进行种群研究。功能界别 这些再生的T细胞群体的能力也是令人感兴趣的。 人类辅助性T细胞对异种MHC编码抗原的反应 通过刺激小鼠细胞群来表达已经被研究并 被发现在评估人类T辅助细胞方面有特殊用途 功能在于这一点
英文摘要
The elimination from marrow of cells expressing T cell surface markers 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. Approaches were developed for depleting normal and malignant T cell marrow populations by using elutriation and deriving monoclonal antibodies specific for cell surface molecules unique to T cells. These approaches were used to develop clinical protocols to assess the feasibility of utilizing allogenic HLA-mismatched, T cell depleted allogeneic marrow and autologous marrow purged of malignant T cells in the treatment of aggressive hematolymphopoietic malignancies. Preclinical studies in rhesus monkeys demonstrated that functional T cell populations are generated in animals receiving T cell depleted autologous marrow. The time course of CD4+ T cell reconstitution and development of in vivo T cell immunocompetence correlated with the number of T cells infused in the marrow, and did not correlate with marrow cell dose or 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. The mechanisms by which infused, mature T cells generate reconstituting peripheral T cell populations is under investigation in murine models. 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
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MARROW GRAFT REJECTION IN ALLOGENEIC BONE MARROW TRANSPLANTATION
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