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

项目总结 整体组件 疫苗是最具成本效益和非常成功的医疗干预措施之一。其中的大多数 疫苗依赖于CD4T+细胞及其对B细胞的帮助。我们对体内、特异性人类CD4+T细胞的理解 细胞对病原体的反应仍然是模糊的，由于生物学的复杂性，细胞的稀有性，相对 难以接近的组织定位，以及识别特定CD4+T细胞的技术挑战。因此，我们的 解决这一严重问题的方法一直是开发多种新技术来研究人类CD4+T细胞 在过去的几年里。虽然依赖于CD4+T细胞的抗体反应一直是保护性的来源 对于大多数获得许可的疫苗(项目1)，有一个非常好的论点，即许多疾病 我们没有成功的疫苗需要适应性免疫反应，而不是抗体来保护 (项目2和项目3)。这里提出的三个项目积极寻求对机制的理解 通过新的实验方法调节人类抗病原体CD4+T细胞。

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.