T CELL FUNCTION IN T CELL DEPLETED STATES

T 细胞耗竭状态下的 T 细胞功能

• 批准号: 5201018
• 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/5201018
• 关键词: MHC class II antigen; Macaca mulatta; T lymphocyte; age difference; antigen presentation; antigen presenting cell; autologous transplantation; bone marrow transplantation; colony stimulating factor; helper T lymphocyte; human subject; immunologic memory; laboratory mouse; leukocyte activation /transformation; lymphocyte proliferation; neoplasm /cancer chemotherapy; phenotype

Mechanisms by which T cell populations are generated are relevant to considerations of immunoreconstitution in situations in which T cell depletion occurs. Studies in rhesus monkeys investigating T cell generation following T cell depleted autologous marrow transplantation provided evidence that residual T cells in infused T cell-depleted marrow play a central role in the generation of subsequent T cell populations. This possibility was confirmed in murine studies in which three T cell progenitor pools were identified which contribute to final T cell repopulation following marrow transplantation. It was found that cells arising from a peripheral, mature lymphocyte precursor pool were of memory phenotype, and that only T cells generated by a thymic pathway contained large numbers of naive T cells. This information has been applied to studies of T cell generation in patients receiving chemotherapy which have shown an age dependence on generation of T cells by the thymus & have provided a paradigm by which T cell generation might be studied in other circumstances. The functional capacities of regenerated T cell populations is also of interest. The human T helper cell response to xenogeneic MHC encoded antigens expressed by stimulating murine cell populations has been studied & 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 & presentation in association with human Class II gene products. The requirement for reprocessing of murine antigen & presentation by responder-type cells (rather than murine stimulating cells) was found to be due to lack of both murine antigen presenting cell activation & responder human T cell activation. Further, GM-CSF provided a sufficient signal to murine APC to result in upregulation of B7-2, enabling murine antigen presenting cells to directly present antigen to human T helper cells.

T细胞群产生的机制与以下因素相关 在T细胞免疫的情况下， 发生了损耗。 恒河猴T细胞研究 去除T细胞的自体骨髓移植后的世代 提供了证据表明，输注的T细胞耗尽的 骨髓在随后的T细胞生成中起着中心作用 人口。 这种可能性在小鼠研究中得到证实， 哪三个T细胞祖细胞库被鉴定出来， 骨髓移植后最终T细胞再增殖。 这是 发现细胞起源于外周成熟淋巴细胞， 前体细胞库具有记忆表型，只有T细胞 由胸腺途径产生的含有大量幼稚T 细胞 这些信息已被应用于T细胞的研究。 在接受化疗的患者中， 胸腺对T细胞生成的依赖性， T细胞生成的范例可能在其他研究中被研究。 情节 再生T细胞的功能 人口也很重要。 人类T辅助细胞对 刺激小鼠细胞表达的异种MHC编码抗原 人口已被研究，并发现在特殊用途， 人T辅助细胞功能的评估， 反应需要对刺激性鼠抗原进行再加工， 与人类II类基因产物相关的呈递。 的 鼠抗原再处理要求 发现了反应型细胞（而不是鼠刺激细胞） 这是由于缺乏鼠抗原呈递细胞活化和 应答人T细胞活化。 此外，GM-CSF提供了一种 向鼠APC发出足够信号以导致B7-2上调， 使鼠抗原呈递细胞能够直接呈递抗原 人类T辅助细胞。