pd-l1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunctionpd-l1封锁改善生存在实验脓毒症通过抑制淋巴细胞凋亡和扭转单核细胞功能障碍.pdfVIP

Zhang et al. Critical Care 2010, 14:R220 /content/14/6/R220 RESEARCH Open Access PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction 1† 2† 3† 3 3 3 3 Yan Zhang , Ying Zhou , Jingsheng Lou , Jinbao Li , Lulong Bo , Keming Zhu , Xiaojian Wan , Xiaoming Deng3*, Zailong Cai1* Abstract Introduction: Lymphocyte apoptosis and monocyte dysfunction play a pivotal role in sepsis-induced immunosuppression. Programmed death-1 (PD1) and its ligand programmed death ligand-1 (PD-L1) exert inhibitory function by regulating the balance among T cell activation, tolerance, and immunopathology. PD-1 deficiency or blockade has been shown to improve survival in murine sepsis. However, PD-L1 and PD-1 differ in their expression patterns and the role of PD-L1 in sepsis-induced immunosuppression is still unknown. Methods: Sepsis was induced in adult C57BL/6 male mice via cecal ligation and puncture (CLP). The expression of PD-1 and PD-L1 expression on peripheral T cells, B cells and monocytes were measured 24 hours after CLP or sham surgery. Additionally, the effects of anti-PD-L1 antibody on lymphocyte number, apoptosis of spleen and thymus, activities of caspase-8 and caspase-9, cytokine production, bacterial clearance, and survival were determined. Results: Expression of PD-1 on T cells, B cells and monocytes and PD-L1 on B cells and monocytes were up- regulated in septic animals compared to sham-operated controls. PD-L1 blockade significantly improved survival of CLP mice. Anti-PD-L1 antibody administration prevented sepsis-induced depletion of lymphocytes, increased tumor necrosis factor (TNF)-a and interleukin (IL)-6 production, decrea