title: Ethylene carbodiimide-fixed donor splenocytes combined with α-1 antitrypsin induce indefinite donor-specific protection to mice cardiac allografts.
abstract: Peritransplant infusion of ethylene carbodiimide-fixed donor splenocytes (ECDI-SPs) induces protection of islet and cardiac allografts. However, pro-inflammatory cytokine production during the peritransplantation period may negate the effect of ECDI-SPs. Therefore, we hypothesized that blocking pro-inflammatory cytokine secretion while increasing levels of anti-inflammatory cytokines would enhance the tolerance-induced efficacy of ECDI-SPs. The objective of this study was to determine the effectiveness of using ECDI-SPs combined with a short course of α1-antitrypsin (AAT) for induction of tolerance. Using a mice cardiac transplant model, we demonstrated that ECDI-SPs + AAT effectively induced indefinite mice cardiac allograft protection in a donor-specific fashion. This effect was accompanied by modulation of cytokines through decreasing levels of pro-inflammatory cytokines (including IFN-γ, TNF-α, IL-1β, IL-6, IL-17, and IL-23) and increasing levels of anti-inflammatory cytokines (including IL-10, IL-13, and TGF-β), and by inhibition of effector T cells (Teff) and expansion of regulatory T cells (Tregs). Therefore, we concluded that combined ECDI-SPs and AAT appeared to modulate the expression of cytokines and regulate the Teff:Treg balance to create a support milieu for graft protection. Our strategy of combining ECDI-SPs and AAT provides a promising approach for inducing donor-specific transplant tolerance.
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Organ Transplantation Department, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Xingqiang
authors.initials: X
authors.lastname: Lai
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Longhui
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Shuangjin
authors.initials: S
authors.lastname: Yu
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics, Preterm Birth Prevention and Treatment Research Unit, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Ning
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.|Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
authors.forename: Lizhong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.|Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002234:Carbodiimides; D017690:Cell Transplantation / Q000379:methods; D016207:Cytokines / Q000235:genetics; D005404:Fixatives; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000009:adverse effects / Q000379:methods*; D007108:Immune Tolerance; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007165:Immunosuppression Therapy / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology* / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage*
chemical_list: D000893:Anti-Inflammatory Agents; D002234:Carbodiimides; D016207:Cytokines; D005404:Fixatives; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin
keywords: cardiac transplantation; ethylene carbodiimide-fixed donor splenocytes; tolerance; α-1 antitrypsin