tailieunhanh - báo cáo hóa học: " Human brain endothelial cells endeavor to immunoregulate CD8 T cells via PD-1 ligand expression in multiple sclerosis"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Human brain endothelial cells endeavor to immunoregulate CD8 T cells via PD-1 ligand expression in multiple sclerosis | Pittet et al. Journal of Neuroinflammation 2011 8 155 http content 8 1 155 JJOURNAL1 OF. NEUROINFLAMMATION RESEARCH Open Access Human brain endothelial cells endeavor to immunoregulate CD8 T cells via PD-1 ligand expression in multiple sclerosis Camille L Pittet1 Jia Newcombe2 Alexandre Prat1 3 and Nathalie Arbour1 Abstract Background Multiple sclerosis MS an inflammatory disease of the central nervous system CNS is characterized by blood-brain barrier BBB disruption and massive infiltration of activated immune cells. Engagement of programmed cell death-1 PD-1 expressed on activated T cells with its ligands PD-L1 and PD-L2 suppresses T cell responses. We recently demonstrated in MS lesions elevated PD-L1 expression by glial cells and absence of PD-1 on many infiltrating CD8 T cells. We have now investigated whether human brain endothelial cells HBECs which maintain the BBB can express PD-L1 or PD-L2 and thereby modulate T cells. Methods We used primary cultures of HBECs isolated from non-tumoral CNS tissue either under basal or inflamed conditions. We assessed the expression of PD-L1 and PD-L2 using qPCR and flow cytometry. Human CD8 T cells were isolated from peripheral blood of healthy donors and co-cultured with HBECs. Following co-culture with HBECs proliferation and cytokine production by human CD8 T cells were measured by flow cytometry whereas transmigration was determined using a well established in vitro model of the BBB. The functional impact of PD-L1 and PD-L2 provided by HBECs was determined using blocking antibodies. We performed immunohistochemistry for the detection of PD-L1 or PD-L2 concurrently with caveolin-1 a cell specific marker for endothelial cells on post-mortem human brain tissues obtained from MS patients and normal controls. Results Under basal culture conditions PD-L2 is expressed on HBECs whilst PD-L1 is not detected. Both ligands are up-regulated under inflammatory conditions. Blocking PD-L1 and PD-L2 leads .