scholarly journals Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Chia-Wei Li ◽  
Seung-Oe Lim ◽  
Weiya Xia ◽  
Heng-Huan Lee ◽  
Li-Chuan Chan ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Activity ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

PD-L1 (Programmed Death Ligand 1) Regulates T-Cell Differentiation to Control Adaptive Venous Remodeling

2021 ◽  
Author(s):  
Yutaka Matsubara ◽  
Luis Gonzalez ◽  
Gathe Kiwan ◽  
Jia Liu ◽  
John Langford ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nude Mice ◽  
Cell Activity ◽  
Vascular Wall ◽  
Wall Thickening ◽  
T Helper ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Helper Type

Objective: Patients with end-stage renal disease depend on hemodialysis for survival. Although arteriovenous fistulae (AVF) are the preferred vascular access for hemodialysis, the primary success rate of AVF is only 30% to 50% within 6 months, showing an urgent need for improvement. PD-L1 (programmed death ligand 1) is a ligand that regulates T-cell activity. Since T cells have an important role during AVF maturation, we hypothesized that PD-L1 regulates T cells to control venous remodeling that occurs during AVF maturation. Approach and results: In the mouse aortocaval fistula model, anti-PD-L1 antibody (200 mg, 3×/wk intraperitoneal) was given to inhibit PD-L1 activity during AVF maturation. Inhibition of PD-L1 increased T-helper type 1 cells and T-helper type 2 cells but reduced regulatory T cells to increase M1-type macrophages and reduce M2-type macrophages; these changes were associated with reduced vascular wall thickening and reduced AVF patency. Inhibition of PD-L1 also inhibited smooth muscle cell proliferation and increased endothelial dysfunction. The effects of anti-PD-L1 antibody on adaptive venous remodeling were diminished in nude mice; however, they were restored after T-cell transfer into nude mice, indicating the effects of anti-PD-L1 antibody on venous remodeling were dependent on T cells. Conclusions: Regulation of PD-L1 activity may be a potential therapeutic target for clinical translation to improve AVF maturation.

scholarly journals Spatial Regulation of T-Cell Signaling by Programmed Death-Ligand 1 on Wireframe DNA Origami Flat Sheets

ACS Nano ◽  
2021 ◽  
Vol 15 (2) ◽  
pp. 3441-3452
Author(s):  
Trixy Fang ◽  
Jonatan Alvelid ◽  
Joel Spratt ◽  
Elena Ambrosetti ◽  
Ilaria Testa ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Signaling ◽  
Dna Origami ◽  
T Cell Signaling ◽  
Programmed Death Ligand 1 ◽  
Spatial Regulation ◽  
Programmed Death

scholarly journals A critical role for the programmed death ligand 1 in fetomaternal tolerance

2005 ◽  
Vol 202 (2) ◽  
pp. 231-237 ◽  
Author(s):  
Indira Guleria ◽  
Arezou Khosroshahi ◽  
Mohammed Javeed Ansari ◽  
Antje Habicht ◽  
Miyuki Azuma ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Critical Role ◽  
Costimulatory Molecule ◽  
Antibody Treatment ◽  
Programmed Death Ligand 1 ◽  
Fetal Survival ◽  
Programmed Death ◽  
Ifn Γ ◽  
Rag 1

Fetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. Blockade of PDL1 signaling during murine pregnancy resulted in increased rejection rates of allogeneic concepti but not syngeneic concepti. Fetal rejection was T cell– but not B cell–dependent because PDL1-specific antibody treatment caused fetal rejection in B cell–deficient but not in RAG-1–deficient females. Blockade of PDL1 also resulted in a significant increase in the frequency of IFN-γ–producing lymphocytes in response to alloantigen in an ELISPOT assay and higher IFN-γ levels in placental homogenates by ELISA. Finally, PDL1-deficient females exhibited decreased allogeneic fetal survival rates as compared with littermate and heterozygote controls and showed evidence of expansion of T helper type 1 immune responses in vivo. These results provide the first evidence that PDL1 is involved in fetomaternal tolerance.

scholarly journals Regulation of T-Cell Chemotaxis by Programmed Death-Ligand 1 (PD-L1) in Dry Eye–Associated Corneal Inflammation

2010 ◽  
Vol 51 (7) ◽  
pp. 3418 ◽  
Author(s):  
Jaafar El Annan ◽  
Sunali Goyal ◽  
Qiang Zhang ◽  
Gordon J. Freeman ◽  
Arlene H. Sharpe ◽  
...  
Keyword(s):  
T Cell ◽  
Dry Eye ◽  
Programmed Death Ligand 1 ◽  
Corneal Inflammation ◽  
Programmed Death ◽  
Cell Chemotaxis

scholarly journals Salmonella Breaks Tumor Immune Tolerance by Downregulating Tumor Programmed Death-Ligand 1 Expression

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 57
Author(s):  
Man-Chin Chen ◽  
Christian Ronquillo Pangilinan ◽  
Che-Hsin Lee
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Immune Escape ◽  
Cell Infiltration ◽  
Tumor Immune Escape ◽  
Programmed Death Ligand 1 ◽  
T Cell Infiltration ◽  
Programmed Death

Immunotherapy is becoming a popular treatment modality in combat against cancer, one of the world’s leading health problems. While tumor cells influence host immunity via expressing immune inhibitory signaling proteins, some bacteria possess immunomodulatory activities that counter the symptoms of tumors. The accumulation of Salmonella in tumor sites influences tumor protein expression, resulting in T cell infiltration. However, the molecular mechanism by which Salmonella activates T cells remains elusive. Many tumors have been reported to have high expressions of programmed death-ligand 1 (PD-L1), which is an important immune checkpoint molecule involved in tumor immune escape. In this study, Salmonella reduced the expression of PD-L1 in tumor cells. The expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), and the phospho-p70 ribosomal s6 kinase (P-p70s6K) pathway were revealed to be involved in the Salmonella-mediated downregulation of PD-L1. In a tumor-T cell coculture system, Salmonella increased T cell number and reduced T cell apoptosis. Systemic administration of Salmonella reduced the expressions of PD-L-1 in tumor-bearing mice. In addition, tumor growth was significantly inhibited along with an enhanced T cell infiltration following Salmonella treatment. These findings suggest that Salmonella acts upon the immune checkpoint, primarily PD-L1, to incapacitate protumor effects and thereby inhibit tumor growth.

Antigen-Specific Transfer of Functional Programmed Death Ligand 1 From Antigen Presenting Cells Onto Human CD8+ T Cells Via Trogocytosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 584-584
Author(s):  
Regina Gary ◽  
Simon Voelkl ◽  
Ralf Palmisano ◽  
Andreas Mackensen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Antigen Presenting Cells ◽  
Programmed Death Ligand 1 ◽  
Cell Responses ◽  
Surface Molecules ◽  
Programmed Death ◽  
Antigen Presenting

Abstract Abstract 584 Specific T-cell responses are initiated by T-cell receptor (TCR) recognition of peptide-MHC-complexes on antigen presenting cells (APCs). Upon specific interaction of T cells with APCs T cells capture membrane fragments and surface molecules of APCs in a process termed trogocytosis. Exchange of membrane molecules/antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. Here, we demonstrate that human antigen-specific CD8+ T cells do acquire the co-inhibitory molecule programmed death ligand 1 (PD-L1) from mature monocyte-derived dendritic cells (mDC) and tumor cells in an antigen-specific manner. The kinetics of PD-L1 transfer revealed a maximal PD-L1 expression on antigen-specific T cells within 3–4 hours after co-incubation with antigen-pulsed APCs, being detectable up to 72 hours. Antigen-pulsed immature DCs were less effective in transfering surface molecules such as PD-L1 onto CD8+ T cells after antigen-specific recognition. Using a transwell system we could show that the acquisition of PD-L1 requires cell-cell contact. Furthermore, PD-L1 cannot be acquired by T cells from a lysate of mDCs. The transfer process is impaired after pretreatment of T cells with concanamycin A, a specific inhibitor of vacuolar ATPases, playing an important role in membrane trafficking. Moreover, fixation of DCs with glutaraldehyde completely abrogated the acquisition of PD-L1 on T cells suggesting that an active interaction between APCs and T cells is required for trogocytosis. Of importance, CD8+ T cells which acquired PD-L1 complexes, were able to induce apoptosis of neighbouring PD-1 expressing CD8+ T cells, that could be completely blocked by an anti-PD-L1 antibody. In summary our data demonstrate for the first time that human antigen-specific CD8+ T cells take up functionally active PD-L1 from APCs in an antigen-specific fashion, leading to apoptosis of PD-1 expressing T cells. The transfer of functionally active co-inhibitory molecules from APCs onto human CD8+ T cells may serve to limit clonal expansion of antigen-specific T-cell responses but may also play a major role for T-cell exhaustion in chronic infection and tumor immunosurveillance. Disclosures: No relevant conflicts of interest to declare.

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