MECHANISMS OF HELP FOR CD8 T CELL RESPONSES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 对许多细胞内病原体的保护是由CD8T细胞提供的，病原体特异性CD8T细胞被认为需要CD4T细胞帮助发育成有效的记忆性CD8T细胞。由于小鼠CD8T细胞不转录MHC-II类基因，一些模型认为抗原提呈细胞(APC)是CD4T细胞向CD8T细胞传递帮助所必需的媒介。我们已经证明了在体外和体内激活的小鼠CD8T细胞上存在MHC II类分子。这些CD8T细胞通过一种被称为巨噬细胞增多的过程，从其激活的APC，特别是CD11c阳性的树突状细胞(DC)获得MHC II类。在活化的小鼠CD8T细胞上转移的MHC-II类分子具有功能活性，并能直接刺激特异性指标CD4T细胞。与“无助”的CD8 T细胞相比，在体外被“帮助”并随后被允许在体内休息的CD8 T细胞在受到攻击时表现出更强的回忆反应；相反，在立即受到攻击时没有看到差异。这些数据表明，CD8：CD4T细胞的直接相互作用可能对CD8T细胞有很大的帮助。此外，这一机制可能使CD8T细胞与相互作用的CD4T细胞的不同亚群进行通信，从而调节免疫反应。这些研究可能会对艾滋病毒/艾滋病的研究产生影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Protection against many intracellular pathogens is provided by CD8 T cells, and pathogen-specific CD8 T cells are thought to need CD4 T cell help to develop into effective memory CD8 T cells. Since murine CD8 T cells do not transcribe MHC class II genes, several models have proposed antigen presenting cells (APCs) as intermediaries required for CD4 T cells to deliver their help to CD8 T cells. We have demonstrates the presence of MHC class II molecules on activated murine CD8 T cells in vitro as well as in vivo. These CD8 T cells acquire MHC class II from their activating APCs, particularly CD11c positive dendritic cells (DCs), via a process called trogocytosis. Transferred MHC class II molecules on activated murine CD8 T cells were functionally competent and could directly stimulate specific indicator CD4 T cells. CD8 T cells that were "helped" in vitro and subsequently allowed to rest in vivo showed enhanced recall responses upon challenge compared to "helpless" CD8 T cells; in contrast, no differences were seen upon immediate challenge. These data indicate that direct CD8:CD4 T cell interactions may significantly contribute to help for CD8 T cells. Furthermore, this mechanism may enable CD8 T cells to communicate with different subsets of interacting CD4 T cells that could modulate immune responses. These studies could have implications for HIV/AIDS research.