DEGRANULATION FUNCTIONS OF CYTOTOXIC T LYMPHOCYTES

细胞毒性 T 淋巴细胞的脱颗粒功能

• 批准号: 3125846
• 负责人: WILLIAM R CLARK
• 金额: $ 16.21万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-09-30 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3125846
• 关键词: cell mediated lymphocytolysis test; cytotoxic T lymphocyte; gene expression; genetic manipulation; granule; helper T lymphocyte; laboratory mouse; leukocyte activation /transformation; lymphokines; plant virus; protein biosynthesis; protein sequence; protein structure function; radiotracer; tissue /cell culture

Cytotoxic T lymphocytes (CTLs) that have been exposed for several days to high concentrations of IL-2 either in vitro or in vivo become highly granular in nature. Considerable attention has been focused on the possibility that these IL-2 induced granules might contain a cytotoxin that could explain how CTLs kill their target cells. How such a mechanism would fit into CTL killing in general is still controversial. What cannot be questioned, however, is that CTLs do not undergo a degranulation process during target cell killing. The contents of CTL granules have been only crudely analyzed. While it is certain that a number of different serine esterases reside in granules, little else is known. We recently began an extensive search for biologically interesting activities released during CTL degranulation. We have defined three activities functionally, and now propose detailed biological, biochemical and molecular genetic analyses of these activities. The three activities we have defined are: CTL inhibition, which is probably a feedback regulatory mechanism for controlling CTL function; T helper cell inhibitin, which may be involved in CD8+ T cell suppression of helper function; and viral inhibitin, which drastically inhibits the ability of mature viral particles to infect cells. Understanding the biochemical basis of these activities will greatly broaden our understanding of CTL function.

细胞毒性T淋巴细胞（CTL）已经暴露了几个 在体外或体内， 变得非常颗粒化。 相当多的关注 一直关注这些IL-2诱导的颗粒 可能含有一种细胞毒素，可以解释CTL是如何杀死他们的 靶细胞 这种机制如何适用于CTL杀伤， 将军仍然有争议。 不能质疑的是， CTL不经历脱粒过程， 在靶细胞杀伤过程中。 CTL颗粒的含量有 只是粗略地分析了一下。 虽然可以肯定， 不同的丝氨酸酯酶存在于颗粒中， 知道的 我们最近开始了一项广泛的生物学研究， CTL脱颗粒过程中释放的有趣活性。 我们 我已经从功能上定义了三项活动，现在提出 详细的生物、生化和分子遗传分析 这些活动。 我们定义的三项活动是： CTL抑制可能是一种反馈调节机制 用于控制CTL功能; T辅助细胞抑制素， 参与辅助功能的CD 8 + T细胞抑制;和 病毒抑制素，它能显著抑制成熟的 病毒颗粒感染细胞。 了解生物化学 这些活动的基础将大大拓宽我们的理解 CTL的功能。