Anti-CD3 antibody treatment induces hypoglycemia and super tolerance to glucose challenge in mice through enhancing glucose consumption by activated lymphocytes

Anti-cd3 antibody has been employed for various immune-mediated disorders. however,whether anti-cd3 administration leads to rapid metabolic alternation has not been well investigated. in the current study,we studied how anti-cd3 treatment affected blood glucose levels in mice. we found that anti-cd3 treatment induced immediate reduction of blood glucose after administration. furthermore,a single dose of anti-cd3 treatment corrected hyperglycemia in all nonobese diabetic mice with recently diagnosed diabetes. this glucose-lowering effect was not attributable to major t cell produced cytokines. of interest,when tested in a normal strain of mice (c57bl/6),the serum levels of c-peptide in anti-cd3 treated animals were significantly lower than control mice. paradoxically,anti-cd3 treated animals were highly tolerant to exogenous glucose challenge. additionally,we found that anti-cd3 treatment significantly induced activation of t and b cells in vitro and in vivo. further studies demonstrated that anti-cd3 treatment lowered the glucose levels in t cell culture media and increased the intracellular transportation of 2-(n-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2 deoxyglucose (2-nbdg) particularly in activated t and b cells. in addition,injection of anti-cd3 antibodies induced enhanced levels of glut1 expression in spleen cells. this study suggests that anti-cd3 therapy-induced hypoglycemia likely results from increased glucose transportation and consumption by the activated lymphocytes. © 2014 chang-qing xia et al.