Differential expansion of gamma delta T cells with

描述（由申请人提供）：研究计划：I型干扰素已被证明可导致牛γ - 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CD8+ γ - T细胞的扩增。I型干扰素诱导树突状细胞产生IL-15，并在小鼠中刺激CD8+ aphabeta T细胞的选择性扩增。小鼠的选择性扩增与细胞表面某些IL-15受体亚基的高密度相关。我们建议研究CD8+ γ δ T细胞在I型干扰素作用下选择性扩增的机制。我们将研究WCI CD8+ γ δ T细胞在I型IFN培养中优先扩增的假设，因为该细胞亚群上IL-15受体的一个或多个亚基的表面表达密度更高。使用牛可以更容易地获得大量的γ - δ T细胞，并提供先前描述的CD8+和CD8群体的γ - δ T细胞在I型干扰素培养中反应不同的系统。该项目将使人们更好地了解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。

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.