Differential expansion of gamma delta T cells

γ δ T 细胞的差异扩增

• 批准号: 6669783
• 负责人: KEVIN K LAHMERS
• 金额: $ 7万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6669783
• 关键词: T lymphocyte; biological signal transduction; cell differentiation; cell proliferation; cellular immunity; cow; cross immunity; cytokine receptors; cytotoxic T lymphocyte; cytotoxicity; enzyme linked immunosorbent assay; flow cytometry; interferons; interleukin 15; interleukin 2; neutralizing antibody; polymerase chain reaction; recombinant proteins; tissue /cell culture

DESCRIPTION (provided by applicant): Research Proposal: Type I interferons have been shown to lead to differential expansion of subsets of gammadelta T lymphocytes in cattle. The mechanism of this expansion has not been identified, but the direct anti-proliferative effect of type I interferons on T lymphocytes indicates that type I interferon must have additional mechanisms to stimulate expansion of CD8+ gammadelta T cells. Type I interferons induce IL-15 production by dendritic cells and have been shown to stimulate selective expansion of CD8+ aphabeta T cells in mice. The selective expansion in mice correlated with higher density of some subunits of the IL-15 receptors on the cell surface. We propose to examine the mechanism(s) of selective expansion of CD8+ gammadelta T cells in response to type I interferon. We will investigate the hypothesis that WCI CD8+ gammadelta T cells preferentially expand in culture with type I IFN as a result of higher density of surface expression of one or more subunits of the IL-15 receptor on this cell subset. The use of cattle allows easier access to high numbers of gammadelta T cells and provides a previously described system with CD8+ and CD8 populations of gammadelta T cells respond differently in culture with type I interferons. This project will allow a better understanding of gammadelta T cell biology with the long-term goal of targeting certain lymphocyte subsets in the development of immune responses. The Candidate: The candidate is a veterinarian completing a residency in comparative anatomical pathology and is a Ph.D. candidate. The candidate has completed most of his pathology residency, didactic course work, and is actively involved in the research phase of a combined residency/PhD program. This proposal constitutes his plan to complete doctoral research focusing on the immunology at Washington State University. Environment: The Department of Veterinary Microbiology and Pathology provides both modern research facilities for infectious disease research and a highly interactive training environment including intra- and interdisciplinary graduate education, residency programs, and extensive collaboration both within and outside the university. The sponsors collaborate closely in research and have successfully mentored clinicians, graduate students, and post-doctoral fellows to research independence.

描述（由申请人提供）：研究方案：I型干扰素已被证明可导致牛γ δ T淋巴细胞亚群的差异扩增。这种扩增的机制尚未确定，但I型干扰素对T淋巴细胞的直接抗增殖作用表明，I型干扰素必须有额外的机制来刺激CD 8 + γ δ T细胞的扩增。I型干扰素诱导树突状细胞产生IL-15，并已显示刺激小鼠中CD 8+无丝T细胞的选择性扩增。小鼠中的选择性扩增与细胞表面上IL-15受体的某些亚基的较高密度相关。我们建议检查CD 8 + γ δ T细胞对I型干扰素应答的选择性扩增的机制。我们将研究的假设，WCI CD 8 + γ δ T细胞优先扩大与I型IFN的培养，作为一个或多个亚基的IL-15受体在这个细胞亚群的表面表达密度较高的结果。牛的使用允许更容易地获得大量的γ δ T细胞，并提供了先前描述的系统，其中γ δ T细胞的CD 8+和CD 8群体在I型干扰素的培养物中响应不同。该项目将允许更好地了解γ δ T细胞生物学，其长期目标是在免疫反应的发展中靶向某些淋巴细胞亚群。 候选人：候选人是一名兽医，完成了比较解剖病理学的住院医师培训，是一名博士。候选人候选人已经完成了他的大部分病理学住院医师，教学课程的工作，并积极参与联合住院医师/博士课程的研究阶段。这一提议构成了他在华盛顿州立大学完成免疫学博士研究的计划。 工作环境：兽医微生物学和病理学系为传染病研究提供了现代化的研究设施，并提供了高度互动的培训环境，包括内部和跨学科的研究生教育，住院医生计划以及大学内外的广泛合作。赞助商在研究方面密切合作，并成功地指导临床医生，研究生和博士后研究员进行独立研究。