Differential expansion of gamma delta T cells with

描述(由申请人提供)：研究建议：I型干扰素已被证明能导致牛体内Gammadelta T淋巴细胞亚群的不同扩张。这种扩增的机制尚不清楚，但I型干扰素对T淋巴细胞的直接抗增殖作用表明，I型干扰素一定有额外的机制来刺激CD8+Gammadelta T细胞的扩张。I型干扰素诱导树突状细胞产生IL-15，并已被证明能刺激小鼠CD8+aphabeta T细胞的选择性扩增。小鼠的选择性扩增与细胞表面IL-15受体某些亚单位密度较高有关。我们建议研究CD8+Gammadelta T细胞选择性扩增对I型干扰素的反应机制(S)。我们将研究WCI CD8+Gammadelta T细胞在I型干扰素的培养中优先扩增的假设，这是由于该细胞亚群上IL-15受体的一个或多个亚单位的表面表达密度较高所致。使用牛可以更容易地获得大量的Gammadelta T细胞，并提供了一个先前描述的系统，CD8+和CD8群体的Gammadelta T细胞在I型干扰素的培养中反应不同。该项目将允许更好地了解Gammadelta T细胞生物学，长期目标是在免疫反应的发展中针对特定的淋巴细胞亚群。 候选人：候选人是一名兽医，完成了比较解剖学病理学的住院医师学位，并且是一名博士候选人。这位候选人已经完成了他的大部分病理实习和授课课程工作，并积极参与了实习/博士相结合的项目的研究阶段。这项提议构成了他在华盛顿州立大学完成专注于免疫学的博士研究的计划。 环境：兽医微生物学和病理学系为传染病研究提供现代化的研究设施和高度互动的培训环境，包括学科内和学科间的研究生教育、住院医师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实现研究独立性。

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.