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Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells.

Abstract：

:Lymphatic endothelial cells (LECs) induce peripheral tolerance by direct presentation to CD8 T cells (T(CD8)). 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 T(CD8), 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 T(CD8) survival. Rescue of tyrosinase-specific T(CD8) 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.

journal_name

Blood

journal_title

Blood

authors

Tewalt EF,Cohen JN,Rouhani SJ,Guidi CJ,Qiao H,Fahl SP,Conaway MR,Bender TP,Tung KS,Vella AT,Adler AJ,Chen L,Engelhard VH

doi

10.1182/blood-2012-04-427013

subject

Has Abstract

pub_date

2012-12-06 00:00:00

pages

4772-82

issue

24

eissn

0006-4971

issn

1528-0020

pii

blood-2012-04-427013

journal_volume

120

pub_type

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