IL 4 DIRECTED IMMUNE RESPONSES TO CAEV SU

IL 4 对 CAEV SU 的定向免疫反应

• 批准号: 2886118
• 负责人: Kevin Roy Snekvik
• 金额: $ 7.1万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2886118
• 关键词: Lentivirus; arthritis; cellular immunity; goats; helper T lymphocyte; interferon gamma; interleukin 4; leukocyte activation /transformation; pathologic process; polymerase chain reaction; recombinant proteins; tissue /cell culture; transfection; virus antigen; virus diseases; virus replication

1. Research Proposal: The proposed research will utilize plasmid expression vectors to initiate a Type 2 immune response to lentiviral envelope proteins and determine if the induced Type 2 immune response leads to the development of clinical disease following homologous virus challenge. The long-term objective of this research is to identify critical lymphocyte-mediated immune effector mechanisms that allow lentiviral replication and initiation of clinical disease in outbred species. The lentiviral system to be studied is caprine arthritis encephalitis virus (CAEV) in goats. Goats become persistently infected with CAEV and either remain asymptomatic or progress to clinical disease characterized by arthritis. Symptomatic goats have intralesional memory and immunoglobulin producing B-lymphocytes, increased serum and synovial fluid titers of polyclonal IgG1 and CAEV SU reactive antibodies, and increased CAEV SU responsive Th2 lymphocytes compared to asymptomatic goats. These findings suggest that clinical disease in CAEV infected goals may be determined by a dominant viral specific type 2 immune response. The proposed specific aims permit investigation of the role of Type 2 cytokines, specifically IL-4, in the initial segregation of the immune response to a Type 2 profile and the progression of disease from lentiviral infections. In specific aim 1, immunization with a mammalian expression vector that encodes CAEV SU in conjunction with a second expression vector encoding IL-4 will be used to stimulate antigen specific T helper lymphocytes and initiate a Type 2 immune response. Documented studies in mice have shown that intramuscular injection of expression vectors that encode IL-4 stimulate the development of Type 2 immune responses to co-immunized viral antigens. In specific aim 2, the immunized goats will be infected with CAEV and disease progression evaluated. Anticipated results will demonstrate the use of recombinant cytokines to focus antigen specific T helper lymphocytes pathways in outbred species and provide an opportunity to directly examine the role of Type 2 responses in a persistent lentivirus infection. 2. Candidate: The candidate is a veterinarian completing a residency in comparative pathology and is a Ph.D candidate. In preparation for research, the candidate has completed graduate courses in biochemistry, molecular biology, mechanism of disease, and immunopathology. This proposal constitutes his doctoral research and will provide an excellent basis for future independent research in lentivirus infections.

1.研究提案：拟议的研究将利用质粒 启动针对慢病毒的2型免疫应答的表达载体 并确定诱导的2型免疫应答是否 导致临床疾病的发展， 挑战. 这项研究的长期目标是确定 关键的淋巴细胞介导的免疫效应机制， 慢病毒复制与远交系动物临床疾病发生 物种 待研究的慢病毒系统是山羊关节炎 山羊脑炎病毒（CAEV）。 山羊会持续感染 与CAEV，并保持无症状或进展到临床疾病 以关节炎为特征。 有症状的山羊有病灶内记忆 和免疫球蛋白产生B淋巴细胞，增加血清和滑膜 多克隆IgG 1和CAEV SU反应性抗体的液体滴度，和 与无症状相比，CAEV SU应答性Th 2淋巴细胞增加 山羊 这些结果表明，CAEV感染者的临床疾病 目标可以由显性病毒特异性2型免疫决定 反应提出的具体目标允许调查的作用 2型细胞因子，特别是IL-4，在最初的分离， 对2型特征的免疫应答和疾病进展 慢病毒感染。 在具体目标1中， 编码CAEV SU的哺乳动物表达载体，其与 编码IL-4的第二表达载体将用于刺激抗原 特异性T辅助淋巴细胞并启动2型免疫应答。 在小鼠中进行的记录研究表明， 编码IL-4的表达载体刺激型 2对共免疫病毒抗原的免疫应答。 在具体目标2中， 免疫山羊将感染CAEV并发生疾病进展 评估。 预期的结果将证明使用重组 细胞因子聚焦抗原特异性T辅助淋巴细胞途径， 远交种，并提供了一个机会，直接检查的作用， 持续性慢病毒感染中的2型反应。 2.候选人： 候选人是一名兽医，完成了比较 病理学博士候选人。 为了准备研究， 候选人已完成生物化学，分子生物学， 生物学、疾病机制和免疫病理学。这项建议 构成了他的博士研究，并将提供一个很好的基础， 用于未来慢病毒感染的独立研究。