ECDI-fixed allogeneic splenocytes combined with α1-antitrypsin prolong survival of rat renal allografts.
Pre- and post-transplant infusions of donor splenocytes treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI-SPs) induce donor-specific tolerance and prolong rat renal allograft survival. However, proinflammatory cytokine production during peritransplantation negates the effects of ECDI-SPs. Therefore, we reasoned that blocking proinflammatory cytokines would promote long-term ECDI-SP-induced allograft survival. We therefore examined the effects of infusing ECDI-SPs alone or in combination with a short course of α1-Antitrypsin (AAT) on the long-term outcomes of a rat kidney allograft model. The data showed that ECDI-SPs+AAT promote renal allograft survival compared with ECDI-SPs alone. This effect was accompanied by expansion of Foxp3+ Tregs, enhanced alloantigen-specific Treg function, and modulation of expression levels of proinflammatory cytokines IL-1β, IL-6, TNF-α, and the anti-inflammatory cytokine IL-10. In conclusion, our strategy of combining ECDI-SPs and AAT provides a promising approach for inducing specific transplant tolerance.
Division of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Guodong
G
Chen
Division of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Jun
J
Li
Division of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Lizhong
L
Chen
Division of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Xingqiang
X
Lai
Division of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. Electronic address: Qiuj5100@126.com.
Jiang
J
Qiu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D017690:Cell Transplantation; D016207:Cytokines / Q000276:immunology; D005022:Ethyldimethylaminopropyl Carbodiimide / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D016030:Kidney Transplantation; D008297:Male; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology*; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*
D016207:Cytokines; D007166:Immunosuppressive Agents; D000515:alpha 1-Antitrypsin; D005022:Ethyldimethylaminopropyl Carbodiimide
Ethylene carbodiimide (ECDI); Immunologic rejection; Immunologic tolerance; Renal transplantation; α1-Antitrypsin(AAT)