Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells
EF Tewalt, JN Cohen, SJ Rouhani… - Blood, The Journal …, 2012 - ashpublications.org
EF Tewalt, JN Cohen, SJ Rouhani, CJ Guidi, H Qiao, SP Fahl, MR Conaway, TP Bender…
Blood, The Journal of the American Society of Hematology, 2012•ashpublications.orgLymphatic endothelial cells (LECs) induce peripheral tolerance by direct presentation to
CD8 T cells (TCD8). We demonstrate that LECs mediate deletion only via programmed cell
death-1 (PD-1) ligand 1, despite expressing ligands for the CD160, B-and T-lymphocyte
attenuator, and lymphocyte activation gene-3 inhibitory pathways. LECs induce activation
and proliferation of TCD8, but lack of costimulation through 4-1BB leads to rapid high-level
expression of PD-1, which in turn inhibits up-regulation of the high-affinity IL-2 receptor that …
CD8 T cells (TCD8). We demonstrate that LECs mediate deletion only via programmed cell
death-1 (PD-1) ligand 1, despite expressing ligands for the CD160, B-and T-lymphocyte
attenuator, and lymphocyte activation gene-3 inhibitory pathways. LECs induce activation
and proliferation of TCD8, but lack of costimulation through 4-1BB leads to rapid high-level
expression of PD-1, which in turn inhibits up-regulation of the high-affinity IL-2 receptor that …
Abstract
Lymphatic endothelial cells (LECs) induce peripheral tolerance by direct presentation to CD8 T cells (TCD8). We demonstrate that LECs mediate deletion only via programmed cell death-1 (PD-1) ligand 1, despite expressing ligands for the CD160, B- and T-lymphocyte attenuator, and lymphocyte activation gene-3 inhibitory pathways. LECs induce activation and proliferation of TCD8, but lack of costimulation through 4-1BB leads to rapid high-level expression of PD-1, which in turn inhibits up-regulation of the high-affinity IL-2 receptor that is necessary for TCD8 survival. Rescue of tyrosinase-specific TCD8 by interference with PD-1 or provision of costimulation results in autoimmune vitiligo, demonstrating that LECs are significant, albeit suboptimal, antigen-presenting cells. Because LECs express numerous peripheral tissue antigens, lack of costimulation coupled to rapid high-level up-regulation of inhibitory receptors may be generally important in systemic peripheral tolerance.
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