| First Author | Tang L | Year | 2019 |
| Journal | Arch Immunol Ther Exp (Warsz) | Volume | 67 |
| Issue | 3 | Pages | 179-187 |
| PubMed ID | 30927016 | Mgi Jnum | J:295835 |
| Mgi Id | MGI:6454574 | Doi | 10.1007/s00005-019-00539-4 |
| Citation | Tang L, et al. (2019) PD-L1 Ameliorates Murine Acute Graft-Versus-Host Disease by Suppressing Effector But Not Regulatory T Cells Function. Arch Immunol Ther Exp (Warsz) 67(3):179-187 |
| abstractText | There is increasing evidence that interaction between programmed death 1 (PD-1) and its ligands PD-1 (PD-L1) plays a critical role in the pathology of acute graft-versus-host disease (aGVHD). However, the role of PD-L1 in the development of aGVHD has been controversial in recent mouse studies. In this study, we carried out studies in a murine aGVHD model to clarify the role of PD-L1 in aGVHD pathogenesis. We found that systemic overexpression of PD-L1 by hydrodynamic gene transfer (HGT) method in vivo ameliorates aGVHD-induced lethality in mice. Systemic overexpression of PD-L1 inhibits the donor T cells activation, effector memory status, as well as Th1 and Th17 cells responses in vivo. In addition, PD-L1 Ig treatment significantly suppressed T cells' proliferation, promoted T cells' apoptosis, and reduced pro-inflammatory cytokines expression by effector T cells in vitro in the stimulation of anti-CD3/CD28 and allogeneic dendritic cells. However, we found that PD-L1 overexpression did not affect Treg cells' differentiation in vivo and in vitro, depletion of Treg cells in PD-L1 HGT recipients did not aggravate aGVHD mortality. Therefore, our results demonstrated that systemic treatment with PD-L1 protein ameliorates aGVHD by suppressing effector but not regulatory T cell function. Our findings suggest that systemic treatment with PD-L1 may be a potential strategy to prevent or ameliorate aGVHD. |
