Only reduced IFN-c and enhanced IL-10 level could not reverse the insulitis. Second, the beginning of treatment maybe should at prediabetic pieriod and the duration of treatment should be longer. Wen Li et al. reported combined treatment with intracenous antihuman CD20 and oral anti-CD3 could delayed diabetes development in prediabetic hCD20 transgenic NOD mice and reversed diabetes in.60% of mice newly diagnosed with diabetes. Further mechanistic studies showed that the combined therapy enhanced the suppressive function of regulatory T-cells, IL-10- and IL-27- producing dendritic cells. They demonstrated that there was a significant reduction of insulitis 1 month after treatment, but at 15 days and 3 months posttreatment, there were no significant differences in cellular infitration in mice treated with anti-hCD20/ oral anti-CD3 compared with those treated with control IgGs. Another recent paper also showed that anti-CD22 immunotherapy can deplete and reprogram B-cells, therapy reversing autoimmne diabetes in naı¨ve NOD mice. C-peptide is a precursor of insulin. Its secretion level directly reflects the functions of pancreatic b-cells. In this study, we determined serum C-peptide level using ELISA and found that Cpeptide level of mice in combined gene intervention group was significantly elevated compared with that of mice in single gene intervention group and in diabetic control group, but still lower than that of mice in the control group. In addition, C-peptide level of mice in IL-10 intervention group, but not IGF-1 intervention group, was higher than that of mice in diabetic group, suggesting that IL-10, but IGF-1, could protect pancreatic b-cells and IGF-1 could enhance the effects of IL-10 gene. In summary, at the onset of T1DM, adenovirus-mediated IL-10 and/or IGF-1 intervention enhanced TWS119 expression of IL-10 and/or IGF-1 in pancreas and serum, which in turn increased the expression of protective Th2-type cytokines in pancreatic b-cells, reduced the level of destructive Th1-type cytokines in pancreatic b-cells, and increased serum Cpeptide level, thus exerting their protective function and rebalancing Th1/Th2 subset cells in pancreatic b-cells. However, IL-10 and/or IGF-1 intervention could not improve blood glucose and body mass and reduce insulitis. This is possibly because that after the onset of T1D, the inflammatory infiltration of islets was very severe and most islet b-cells had been damaged. Although genetic intervention had certain immunomodulatory and protective roles to islet cells, it could not completely prevent insulitis process, improve the clinical manifestations of diabetes such as enhanced blood glucose and body weight. The study suggested that effects of “cocktail therapy” of combined genetic intervention of IL-10 and IGF-1 were not satisfactory and other more effective cocktail therapies need to be further explored. Specific granule deficiency is a rare congenital disorder caused by a defect in formation of peroxidase negative neutrophil granules.