CD137 SIGNALS IN DC DURING AG-PRIMING INDUCES TOLERANCE

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We confirmed in LCMV infected mice that anti-CD137-meidated suppression can be induced in CD8 T cells, as well as CD4 T cells. Using P14 TCR transgenic T cells and CD137-deficient mice we have shown that the induction of suppression caused by anti-CD137 is independent of CD137 expression on T cells, and that the targeted cell type could be a subset of dendritic cells. Crosslinking of CD137 on these DC was found to induce Stat3 phosphorylation, an event known to suppress DC and B cell maturation and function. Our studies focus on the cellular basis that underlies the induction of immune suppression following injection of agonistic anti-CD137. We also confirmed in an influenza virus infection and survival model that anti-CD137 injected mice experienced an 80% mortality rate whereas using the same infectious dose, only 20% of control mice succumbed to infection.