Marked prolongation of murine cardiac allograft survival using recipient immature dendritic cells loaded with donor-derived apoptotic cells.
We investigated whether recipient dendritic cells (DCs), pretreated with nuclear factor-kappaB oligodeoxyribonucleotide decoy (NF-kappaB ODN decoy) and loaded with ultraviolet B-irradiated donor apoptotic splenocytes (Apo-SCs), were able to induce murine cardiac allograft tolerance. Heterotopic vascularized heart transplantation was performed from BALB/c to C57BL/6 mice, and recipients (C57BL/6) were given one injection of recipient DCs pretreated with NF-kappaB ODN decoy and loaded with donor (BALB/c) apoptotic SCs (decoy Apo-SCs DCs) through the portal vein at 7 days, before heart transplantation in the absence of immunosuppression. The cardiac allograft survival time and the expressive levels of intragraft cytokine genes [interleukin (IL)-2, IL-10, and interferon-gamma] were evaluated. Our results indicated that injection of decoy Apo-SCs DCs significantly prolonged vascularized heart allograft survival and led to skewing of intragraft cytokine expression towards T helper 2 (IL-10). The mechanisms can be useful for therapy of allograft rejection with minimization of systemic immunosuppression.
Xu
Dong-Liang
DL
Department of Urology and Center of Renal Transplantation, Shanghai First People's Hospital, Shanghai, China.
Liu
Yong
Y
Tan
Jian-Ming
JM
Li
Bo
B
Zhong
Cui-Ping
CP
Zhang
Xin-Hua
XH
Wu
Chao-Qun
CQ
Tang
Xiao-Da
XD
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006082:Graft Enhancement, Immunologic / Q000379:methods*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
D007376:Interleukin-2; D008565:Membrane Proteins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10; D007371:Interferon-gamma