Immunosuppressive and protective effects of human α1-antitrypsin on pancreatic β-cell transplantation

AIM：To study the immunosuppressive and protective effects of human α1-antitrypsin (hAAT) on pancreatic β-cell transplantation. METHODS： An NIT-1 cell line (NIT-hAAT) was constructed, which can stably express the protein of hAAT. The BALB/c mice were intraperitoneally injected with NIT-1 and NIT-hAAT cell lines twice to induce cytotoxic T-lymphocytes (CTL). The apoptotic situation, the cytokine expression, and the mRNA expression of inflammatory factors were examined after mixed culture of CTL with NIT-1or NIT-hAAT cell line pretreated with mitomycin. Both cell lines were transferred into the left renal capsule of the diabetic mice to dynamically observe the changes of blood sugar and body weight, the serum levels of insulin and C-peptide, and the pathological changes of the transplanted sites. RESULTS： The results of extended CTL killing assay showed that the cytotoxic effect on NIT-hAAT cell acceptor mice was significantly reduced compared with NIT-1 cell acceptor mice. hAAT effectively reduced apoptosis, inhibited the mRNA expression of inflammatory factors IL-1β and IL-6, and adjusted the balance of Th1/Th2 cytokine expression. After NIT-hAAT was transplanted into the diabetic mice, blood glucose decreased obviously and maintained for 28 d. The serum levels of insulin and C-peptide increased obviously. The infiltration of the inflammatory cells in the transplanted sites significantly reduced. CONCLUSION：hAAT has the abilities of reducing cytotoxic effect of CTL on the β-cells, inhibiting inflammatory factor expression, and stopping short-term immunological rejection of the acceptor. hAAT has obvious immunosuppressive and protective effects on pancreatic β-cell transplantation for treatment of diabetes.