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2 results on '"Shunsuke Ohori"'

1. Overexpression of PD-1 on T cells promotes tolerance in cardiac transplantation via ICOS-dependent mechanisms

Author

Thiago J. Borges, Naoka Murakami, Isadora T. Lape, Rodrigo B. Gassen, Kaifeng Liu, Songjie Cai, Joe Daccache, Kassem Safa, Tetsunosuke Shimizu, Shunsuke Ohori, Alison M. Paterson, Paolo Cravedi, Jamil Azzi, Peter T. Sage, Arlene H. Sharpe, Xian C. Li, and Leonardo V. Riella

Subjects
Immunology, Transplantation, Medicine
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.

Published
2021
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2. Overexpression of PD-1 on T cells promotes tolerance in cardiac transplantation via ICOS-dependent mechanisms

Author

Shunsuke Ohori, Tetsunosuke Shimizu, Isadora T Lape, Leonardo V. Riella, Joe Daccache, Jamil Azzi, Thiago J Borges, Paolo Cravedi, Alison M. Paterson, Kassem Safa, Songjie Cai, Arlene H. Sharpe, Rodrigo Benedetti Gassen, Kaifeng Liu, Xian C Li, Naoka Murakami, and Peter T. Sage

Subjects
T-Lymphocytes, Immunology, Programmed Cell Death 1 Receptor, T cells, Inhibitory postsynaptic potential, medicine.disease_cause, Inducible T-Cell Co-Stimulator Protein, Mice, Immune system, Influenza A virus, Animals, Humans, Medicine, Transplantation, Costimulation blockade, Mechanism (biology), business.industry, Allograft Tolerance, General Medicine, Survival Analysis, Disease Models, Animal, Tolerance induction, Costimulation, Cancer research, Heart Transplantation, business, Tolerance, Research Article
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.

Published
2021

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