IL 4 DIRECTED IMMUNE RESPONSES TO CAEV SU

1.研究建议：建议的研究将利用质粒 启动慢病毒2型免疫应答的表达载体 包膜蛋白和确定是否诱导的2型免疫反应 导致同源病毒后的临床疾病的发展 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允许 慢病毒复制与近交系临床疾病的发病 物种。将要研究的慢病毒系统是山羊关节炎 山羊脑炎病毒(CAEV)。山羊会被持续感染 患有CAEV，要么保持无症状，要么进展到临床疾病 以关节炎为特征的。有症状的山羊有局部性记忆 和免疫球蛋白产生B淋巴细胞，增加血清和滑膜 多克隆IgG1和CAEV SU反应性抗体的液体滴度，以及 与无症状相比，CAEV SU反应性Th2淋巴细胞增加 山羊。这些发现提示临床上感染CAEV的疾病 目标可能由占主导地位的病毒特异性2型免疫决定 回应。拟议的具体目标允许对角色进行调查 2型细胞因子，特别是IL-4，在最初的分离中 对2型的免疫反应与疾病进展 慢病毒感染。在具体目标1中，用一种 编码CAEV SU的哺乳动物表达载体 编码IL-4的第二个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型免疫反应。 对小鼠的有记录的研究表明，肌肉注射 编码IL-4的表达载体刺激类风湿关节炎的发生 2联合免疫病毒抗原的免疫应答。在具体目标2中， 免疫后的山羊将感染CAEV并病情进展 已评估。预期的结果将证明使用重组 细胞因子对抗原特异性辅助性T淋巴细胞通路的作用 并提供了一个直接研究其作用的机会 在持续的慢病毒感染中的2型反应。2.候选人： 应聘者是一名完成比较性实习的兽医。 他是一名病理学博士研究生。在为研究做准备时， 应聘者已经完成了生物化学、分子生物学的研究生课程 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。

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.