B7-H1 agonists could prevent disseminated inflammation by desensitizing cell susceptibility to cytotoxic T-cells
Autor: | Weiwei Yu, Ling Chen, Sizheng Guo, Liqun Luo, Lieping Chen |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: | |
Zdroj: | OncoImmunology, Vol 7, Iss 11 (2018) |
Druh dokumentu: | article |
ISSN: | 2162-402X 2162402X |
DOI: | 10.1080/2162402X.2018.1504156 |
Popis: | The B7-H1/PD-1 immune co-inhibitory pathway is functionally bi-directional. We showed previously that B7-H1 could be widely induced on various types of cells and, in addition to be a ligand for PD-1 on T-cells, also serve as an anti-apoptotic receptor upon interacting with PD-1. We explored the role of B7-H1 as a receptor in protecting allogeneic T-cell mediated host cell destruction and systemic inflammation using mouse models of graft-versus-host disease (GVHD). Administer of by PD-1Ig or a B7-H1 monoclonal antibody (mAb) led to accelerated progression and rapid death in mice transferred with wild type allogeneic T-cells, supporting a dominant role of this pathway in the suppression of allogeneic T-cell response. In sharp contrast, PD-1Ig or B7-H1 mAb could behave as the B7-H1 agonists and drastically ameliorate the progression of GVHD and induced long-term tolerance in the context of transferring PD-1 deficient allogeneic T-cells. We further demonstrated that B7-H1 agonists decreased susceptibility of normal hematopoietic cells to allogenic T-cell lysis in vitro and in vivo. More importantly, mice that developed tolerance could still mount graft-versus-leukemia response. Our findings indicate a role for intrinsic B7-H1 in protecting host cells during systemic inflammation and have implications for treating human diseases including GVHD. |
Databáze: | Directory of Open Access Journals |
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