Impact of Tax on Dendritic Cell Immunologic Function

税收对树突状细胞免疫功能的影响

基本信息

批准号：
6692849
负责人：
KATE M MOSTOLLER
金额：
$ 2.17万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-08-01 至 2004-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6692849
关键词：
Escherichia coli clinical research cytotoxic T lymphocyte dendritic cells enzyme linked immunosorbent assay flow cytometry gel mobility shift assay human T cell lymphotropic virus type 1 human tissue leukocyte activation /transformation predoctoral investigator protein structure function spastic paralysis tissue /cell culture virus protein

项目摘要

DESCRIPTION (provided by applicant): Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of both adult T cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAMKSP). Although the genesis of HAM/TSP likely involves several steps, the generation of a highly specific and effective population of Tax-specific CD8+ cytotoxic T lymphocytes (CTLs) that migrate to the central nervous system (CNS) is of central importance in the genesis of neurologic disease. Presentation of antigenic Tax peptides by mature dendritic cells (DCs) to CD8+ T cells likely plays an important role in the induction of a Tax-specific CTL response. The central hypothesis of the proposed studies is that Tax induces functional alterations in DCs causing their maturation and activation, thus increasing the efficiency of CDS+ T cell activation and leading to the generation of a highly reactive Tax-specific CTL compartment that participates in the genesis of HAM/TSP. The specific aims of the study are to examine the (1) effect of Tax on the activation of murine dendritic cells and primary human peripheral blood-derived dendritic cells; (2) effect of Tax on the immunologic function of murine dendritic cells and primary human peripheral blood-derived dendritic cells; and (3) the pathway and mechanism by which Tax induces dendritic cell maturation.

描述（由申请人提供）：人类T细胞白血病病毒I型（HTLV-I）是成年T细胞白血病（ATL）和HTLV-I-I-I-I-I-CEPIAS相关性脊髓病/热带痉挛性副作用（HAMKSP）的病因。尽管HAM/TSP的起源可能涉及多个步骤，但迁移到中枢神经系统（CNS）的高度特异性和有效的税收特异性CD8+细胞毒性T淋巴细胞（CTL）的产生在神经疾病的创造中至关重要。成熟的树突状细胞（DC）向CD8+ T细胞表达抗原税肽可能在诱导特异性CTL反应的诱导中起重要作用。拟议研究的中心假设是，税收诱导DC的功能改变，导致其成熟和激活，从而提高CDS+ T细胞激活的效率，并导致产生高度反应性的税收特异性CTL室，以参与HAM/TSP的创造。该研究的具体目的是检查（1）税对鼠树突状细胞激活和原发性人外围血液衍生的树突状细胞的激活；（2）税收对鼠树突状细胞和原发性人外周血液衍生的树突状细胞的免疫功能的影响；（3）税收诱导树突状细胞成熟的途径和机制。