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-antitrysin (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.

CITATION INFORMATION: Chen G, Lai X, Qiu L, Zhao Y, Yu S, Zhang J, Chen L. Ethylene Carbodiimide Fixed Donor Splenocytes Combined with α-1 Antitrypsin Induce Indefinite Donor Specific Protection to Mice Cardiac Allografts. Am J Transplant. 2017;17 (suppl 3).

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