CD4-Dependent help for mucosal vaccine responses

肺部感染的真菌病原体，肺孢子虫jirovecii，是一种常见的，往往是致命的 HIV感染的并发症。新出现的数据表明肺孢子虫也可能使肺部疾病复杂化 在未感染艾滋病毒的宿主中。该计划的长期目标是开发一种疫苗， 肺孢子虫为此，我们已经确定了一种新的候选疫苗肺囊虫称为minikexin。 我们将确定CD 4 + T淋巴细胞参与全身和粘膜免疫的机制。 对科兴疫苗的免疫反应。本课题旨在验证CD 4 + T淋巴细胞 对于最佳粘膜CD 8 + T细胞和抗体对mini-kexin应答， 初免/加强疫苗策略。这些研究的目的是确定CD 4 + T淋巴细胞在 正常宿主的疫苗反应。它们是为了补充项目2中提出的实验， 将专注于CD 4非依赖性疫苗反应。除了迷你科信，我们还将投资我们的 通过Anfigen Discovery Core识别的模型系统抗原候选物。 有四个具体目标： 1.为了验证在mini-kexin的启动阶段，CD 4 + T淋巴细胞的帮助是必要的概念， 接种疫苗以获得肺组织中的最佳CD 8+和抗体应答。 2.为了检验T淋巴细胞CD 40配体相互作用对于最佳的CD 8+和 肺裂中的抗体疫苗应答。 3.为了验证Stat 3和IL-17分泌性T淋巴细胞是最佳CD 8+和IL-17分泌性T淋巴细胞所必需的概念， 肺裂中的抗体疫苗应答。 4.验证分泌CD 40+和IL-17的T淋巴细胞在非人的局部疫苗应答中的作用。 灵长类动物

Pulmonary infection with the fungal pathogen, Pneumocystis jirovecii, is a common and often fatal complicafion of HIV infection. Emerging data suggest that Pneumocystis may also complicate lung diseases in non-HIV-infected hosts. The long-term goal of this Program Project is to develop a vaccine against Pneumocystis. To that end, we have identified a novel vaccine candidate for Pneumocysfis termed minikexin. We will identify mechanisms through which CD4+ T-lymphocytes participate in systemic and mucosal immune responses to the kexin vaccine. This project will test the experimental hypothesis that CD4+ Tlymphocyte help is necessary for optimal mucosal CD8+ T-cell and antibody responses to mini-kexin using a prime/boost vaccine strategy. The goal of these studies will be to define the role of CD4+ T-lymphocytes in vaccine responses in normal hosts. They are meant to complement experiments proposed for Project 2 that will focus on CD4-independent vaccine responses. In addition to mini-kexin, we will also invesfigate in our model systems antigen candidates identified through the Anfigen Discovery Core. There are 4 Specific Aims: 1. To test the concept that CD4+ T-lymphocyte help is necessary during the priming phase of mini-kexin vaccination for optimal CD8+ and anfibody responses in lung tissue. 2. To test the concept that T-lymphocyte CD40 ligand interactions are necessary for optimal CD8+ and anfibody vaccine responses in lung fissue. 3. To test the concept that Stat3 and IL-17-secrefing T-lymphocytes are required for optimal CD8+ and anfibody vaccine responses in lung fissue. 4. To validate the role of CD40+ and IL-17-secrefing T-lymphocytes in local vaccine responses of nonhuman primates.