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。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 针对许多细胞内病原体的保护作用由CD 8 T细胞提供，并且病原体特异性CD 8 T细胞被认为需要CD 4 T细胞帮助才能发育成有效的记忆性CD 8 T细胞。由于鼠CD 8 T细胞不转录MHC II类基因，因此几种模型已经提出抗原呈递细胞（APC）作为CD 4 T细胞向CD 8 T细胞递送其帮助所需的中介。我们已经证明了MHC II类分子在体外和体内活化的鼠CD 8 T细胞上的存在。这些CD 8 T细胞通过一种称为胞刺的过程从其活化的APC，特别是CD 11 c阳性树突状细胞（DC）获得MHC II类。活化的小鼠CD 8 T细胞上的转移的MHC II类分子具有功能活性，并且可以直接刺激特异性指示剂CD 4 T细胞。与“无助的”CD 8 T细胞相比，在体外“帮助”并随后允许在体内休息的CD 8 T细胞在激发时显示增强的回忆反应;相反，在立即激发时没有观察到差异。这些数据表明，直接的CD 8：CD 4 T细胞相互作用可能显著有助于CD 8 T细胞。此外，这种机制可以使CD 8 T细胞与可以调节免疫应答的相互作用的CD 4 T细胞的不同子集进行通信。这些研究可能对艾滋病毒/艾滋病研究产生影响。

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.