@article{f3ae91ef3c0d46f2b5c1a8aa9a039ea2,
title = "Overexpression of PD-1 on T cells promotes tolerance in cardiac transplantation via ICOS-dependent mechanisms",
abstract = "The programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is a potent inhibitory pathway involved in immune regulation and is a potential therapeutic target in transplantation. In this study, we show that overexpression of PD-1 on T cells (PD-1 Tg) promotes allograft tolerance in a fully MHC-mismatched cardiac transplant model when combined with costimulation blockade with CTLA-4–Ig. PD-1 overexpression on T cells also protected against chronic rejection in a single MHC II–mismatched cardiac transplant model, whereas the overexpression still allowed the generation of an effective immune response against an influenza A virus. Notably, Tregs from PD-1 Tg mice were required for tolerance induction and presented greater ICOS expression than those from WT mice. The survival benefit of PD-1 Tg recipients required ICOS signaling and donor PD-L1 expression. These results indicate that modulation of PD-1 expression, in combination with a costimulation blockade, is a promising therapeutic target to promote transplant tolerance.",
author = "Borges, {Thiago J.} and Naoka Murakami and Lape, {Isadora T.} and Gassen, {Rodrigo B.} and Kaifeng Liu and Songjie Cai and Joe Daccache and Kassem Safa and Tetsunosuke Shimizu and Shunsuke Ohori and Paterson, {Alison M.} and Paolo Cravedi and Jamil Azzi and Sage, {Peter T.} and Sharpe, {Arlene H.} and Li, {Xian C.} and Riella, {Leonardo V.}",
note = "Funding Information: This work was supported by the following: a research grant from the American Heart Association (AHA) Career Development Award (12FTF12070328) to LVR, National Institute of Health (NIH) grants R01 AI143887 (to LVR), P01 AI056299 (to AHS and PTS), and T32 DK007527 (to NM). This work was supported in part by the Assistant Secretary of Defense and Health Affairs, through the Reconstructive Transplant Research, under award W81XWH2010758 (to LVR). Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. TJB is a recipient of a postdoctoral fellowship grant from the AHA (20POST35210659). This study was supported in part by the Harold and Ellen Danser Endowed Chair in Transplantation at Massachusetts General Hospital. Cartoons were created with BioRender.com. Publisher Copyright: Copyright: {\textcopyright} 2021, Borges et al.",
year = "2021",
month = dec,
day = "22",
doi = "10.1172/jci.insight.142909",
language = "English (US)",
volume = "6",
journal = "JCI insight",
issn = "2379-3708",
publisher = "American Society for Clinical Investigation",
number = "24",
}