Combination of double negative T cells and anti-thymocyte serum reverses type 1 diabetes in NOD mice

Tianhui Liu, Min Cong, Guangyong Sun, Ping Wang, Yue Tian, Wen Shi, Xinmin Li, Hong You, Dong Zhang

Double-negative (DN) T cells could delay the onset and the progression of autoimmune diabetes, yet they were less efficient on reversing autoimmune diabetes. The aim of this study was to investigate whether the combination of DN T cells and anti-thymocyte serum (ATS) could reverse new-onset diabetes in NOD mice. The regulation of different subsets of T cells in vitro and in vivo by ATS and DN T cells were examined using flow cytometry. At the day of diabetes onset, ATS was administered on the same day and 2 days later, and DN T cells were transferred at day 7. The reversion of diabetes was assessed by monitoring blood glucose levels. The efficacy of inhibition of DN T cells on CD8(+) T cells was lower than that on CD4(+) T cells both in vitro and in vivo. ATS resulted in a significant depletion of CD8(+) T cells, while DN T cells were less sensitive to ATS depletion. 80 % diabetic NOD mice achieved long term (6 months) reversion of diabetes by combined ATS and DN T cells treatment, compared to 16 % in ATS single treatment and none in DN T cell single treatment. DN T cells preferentially resided in spleen and pancreatic draining lymph nodes in ATS plus DN T cells treated NOD mice. DN T cells plus ATS therapy show promising reversion effects on diabetic NOD mice due to a shift of balance from a destructive T cell response to one that favors DN T cell regulation.