Transplantation of NIT-1 Cells Expressing pD-L1 for Treatment of Streptozotocin-Induced Diabetes
| Autor: | Daofeng Yang, Guanxin Shen, Li Li, Huifen Zhu, Li Yan, Xue Wen, Min Wang, Jing Liu, Wenjun Liao |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Proliferation index Mitomycin Islets of Langerhans Transplantation Apoptosis Mice Transgenic Ligands B7-H1 Antigen Diabetes Mellitus Experimental Flow cytometry Mice Immune system In vivo Insulin-Secreting Cells Internal medicine medicine Animals Lymphocytes Mice Inbred BALB C Transplantation Membrane Glycoproteins medicine.diagnostic_test business.industry Graft Survival Peripheral tolerance Streptozotocin Coculture Techniques Endocrinology B7-1 Antigen Cancer research Female Peptides business medicine.drug |
| Zdroj: | Transplantation. 86:1596-1602 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/tp.0b013e31818c6e64 |
| Popis: | Background Programmed death-1 ligand-1 (PD-L1, CD274, B7-H1) has been identified as the ligand for the immunoinhibitory receptor programmed death-1 and has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. In this study, we tested the effect of PD-L1-transfected pancreatic beta-cell line established from a transgenic NDD/Lt mouse (NIT) on the alloresponse and streptozotocin-induced diabetes. Methods The diabetes model was established by a low dose of streptozotocin in Balb/C mice. PD-L1 transfected NIT cell line was established, namely NIT-PD-L1. NIT-1, empty vector-transfected NIT-1, or NIT-PD-L1 cells were transplanted into diabetic mice by intraperitoneal injection, respectively. Proliferation and apoptosis of splenic lymphocytes were detected by labeling with carboxy fluorescein succinimidyl ester or AnnexinV-Cy5 and proliferation index (PI). Cytokines were determined by enzyme-linked immunosorbent assay and flow cytometry analysis. Results When compared with the controls, overexpression of PD-L1 on NIT-1 cells markedly prolonged allograft survival in diabetic mice. In mixed cells reaction, splenic lymphocytes from NIT-PD-L1-transplanted diabetic mice co-culture with mitomycin C-treated NIT-PD-L1 showed the lowest proliferative response but severe apoptosis. In addition, NIT-PD-L1 suppressed interferon-gamma but up-regulated interleukin-4 and -10 productions by those lymphocytes in vitro and in vivo. Conclusion Our data demonstrated that overexpression of PD-L1 on pancreatic beta cells significantly can prolong allograft survival, and it is associated with inhibition of lymphocytes activation and proliferation, induction of lymphocytes apoptosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|