Our previous study have shown that infusions of donor splenocytes fixed with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI-SPs) could prolong allografts survival in mice cardiac transplantation model. However, proinflammatory factors(IL-6, IFN-γ and TNF-α) increased dramatically in the allografts that failed to be tolerated, this suggested proinflammatory factors could be important obstacles for tolerance induction. α-1 antitrypsin has been reported to effectively reduce the secretion of proinflammatory factors. In this study we found that combined α-1 antitrypsin and ECDI-SPs could provide indefinite cardiac allografts survival in 100% of recipients. Proinflammatory factors in serum and allografts were significantly lower in α-1 antitrypsin group. ECDI-SPs combined with α-1 antitrypsin could induce more Tregs in vivo compared to ECDI-SPs only. ECDI-SPs could suppress the mixed leucocytes reaction of donor and recipient T cells in vitro by inducing Tregs and secretion of high level of IL-10, which could be dampened by adding proinflammatory factors. α-1 antitrypsin could restore the suppressive function of ECDI-SPs by suppress proinflammatory factors in vitro. These findings suggested that ECDI-SPs combined with α-1 antitrypsin could serve as a promising strategy for promoting immune tolerance in transplantation.

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