CD4 T cell-induced, bid-dependent apoptosis of cutaneous dendritic cells regulates T cell expansion and immune responses
CD4 T cell-induced, bid-dependent apoptosis of cutaneous dendritic cells regulates T cell expansion and immune responses
复制标题
DOI：
10.4049/jimmunol.177.9.5956
复制
发表时间：
2006-11-01
影响因子：
4.4
通讯作者：
Timares, Laura
中科院分区：
文献类型：
--
作者：
Pradhan, Sanjay;Genebriera, Joseph;Timares, Laura
银呈递后树突状细胞（DC）的命运可能是DC亚群特异性的，受许多因素控制。激活诱导的凋亡在调节DC功能中的作用尚不清楚。我们研究了皮肤dc (cdc)，特别是朗格汉斯细胞（LCs）的命运，并观察到它们在成功将Ag呈递到CD4 T细胞后发生凋亡。caspase特异性抑制剂显示LC系在响应CD4 T细胞时使用II型凋亡途径。为了支持这一点，bh3相互作用域（Bid）蛋白在ag特异性T细胞存在下高水平存在并特异性切割。OT-2 CD4细胞对Bid敲除（KO） lc的凋亡也有明显的抵抗。为了验证Bid是否需要在体内调节LC功能，我们测量了Bid KO小鼠的接触致敏和局部免疫反应，并观察到与野生型小鼠相比，Bid KO小鼠的耳部肿胀和增殖反应明显增强。此外，当将ag脉冲Bid KO迁移性cDCs接种到野生型受体中时，观察到表达ifn - γ的扩增OT-2 T细胞的比率和百分比均有所增加。因此，增强的Ag呈现功能是Bid KO cdc所固有的。因此，Bid是LC活力和Ag呈现函数的重要调节因子。
The fate of dendritic cells (DCs) after Ag presentation may be DC subset-specific and controlled by many factors. The role of activation-induced apoptosis in regulating DC function is not clear. We investigated the fate of cutaneous DCs (cDCs), specifically Langerhans cells (LCs), and observed that they undergo apoptosis after successful Ag presentation to CD4 T cells. Caspase-specific inhibitors revealed that LC lines use a type II poptosis pathway in response to CD4 T cells. In support of this, BH3-interacting domain (Bid) protein was present at high levels and specifically cleaved in the presence of Ag-specific T cells. Significant resistance to apoptosis by OT-2 CD4 cells was also observed for Bid knockout (KO) LCs in vitro. To test whether Bid was required to regulate LC function in vivo, we measured contact sensitization and topical immunization responses in Bid KO mice and observed markedly enhanced ear swelling and proliferation responses compared with wild-type mice. Furthermore, when Ag-pulsed Bid KO migratory cDCs were inoculated into wild-type recipients, an increase in both the rate and percentage of expanded OT-2 T cells expressing IFN-gamma was observed. Thus, enhanced Ag presentation function was intrinsic to Bid KO cDCs. Therefore, Bid is an important regulator of LC viability and Ag presentation function.