Endoplasmic reticulum stress-mediated apoptosis involved in indirect recognition pathway blockade induces long-term heart allograft survival.
Implementation of dendritic cell- (DC-) based therapies in organ transplantation can reduce dependency on nonspecific immunosuppression. Despite extensive research, mechanisms of equipped DCs inducing transplant tolerance remain incomplete. Here, we applied RNA interference technique to inhibit CD80 and CD86 expression in host bone marrow-derived DCs. This approach could specifically and effectively knock down CD80 and CD86 expression. T cells primed by these DCs inhibited allogeneic responses. Administration of recipient DCs loaded with alloantigen after CD80 and CD86 blockade prolonged cardiac allograft survival. We also found a higher percentage of apoptotic T cells in lymph tissues and grafts than that detected in control group. In addition, these T cells expressed high expression of GRP78 than controls, indicating activation of unfolded protein responses. Upregulation of CHOP expression among these cells suggested that the endoplasmic reticulum stress (ERS) response switched to a proapoptotic response. Our results indicated that ERS-induced apoptosis may be involved in allogeneic T-cell apoptosis, and the ERS-mediated apoptosis pathway may be a novel target in clinical prevention and therapy of allograft rejection.
Xiang
Jianbin
J
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Gu
Xiaodong
X
Qian
Shiguang
S
Chen
Zongyou
Z
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics; D001854:Bone Marrow Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000276:immunology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation; D007519:Isoantigens / Q000276:immunology; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D034622:RNA Interference; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013312:Stress, Physiological / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic; D014184:Transplantation, Homologous
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D007519:Isoantigens