Functional and dysfunctional human CD4 T cell and B cell responses to bacteria and viruses

项目摘要 总体组件 疫苗是最具成本效益和非常成功的医疗干预措施之一。大多数这些 疫苗依赖于CD4 T+细胞及其对B细胞的帮助。我们对体内特异性人CD4+ T细胞的理解 由于生物学的复杂性，细胞的稀有性， 难以接近的组织定位和鉴定特异性CD4+ T细胞的技术挑战。所以我们的 解决这一严重问题的方法是开发多种新技术来研究人类CD4+ T细胞 在过去的几年里。虽然CD4+ T细胞依赖性抗体反应是保护的来源， 对于大多数获得许可的疫苗（项目1），有一个很好的论点，即许多疾病， 我们没有成功的疫苗，需要抗体以外的适应性免疫反应来保护 （项目2和3）。这里提出的三个项目大力追求对机制的理解 调节人类抗病原体CD4+ T细胞，通过新的实验方法连接。

PROJECT SUMMARY Overall Component Vaccines are one of the most cost effective and extraordinarily successful medical interventions. Most of those vaccines depend on CD4 T+ cells and their help to B cells. Our understanding of in vivo, specific human CD4+ T cell responses to pathogens remains hazy, due to the complexity of the biology, the rarity of the cells, relatively inaccessible tissue localization, and technical challenges of identifying specific CD4+ T cells. Therefore, our approach to this serious problem has been to develop multiple new techniques to study human CD4+ T cells over the past several years. While CD4+ T cell-dependent antibody responses have been the source of protection for most licensed vaccines (Project 1), there is a very good argument to be made that many of the diseases for which we do not have successful vaccines require adaptive immune responses beyond antibodies for protection (Projects 2 and 3). The three Projects proposed here vigorously pursue an understanding of the mechanisms regulating human anti-pathogen CD4+ T cells, linked by new experimental approaches.