Anti-CD3 antibody treatment induces hypoglycemia and super tolerance to glucose challenge in mice through T cell activation (P5218)

Abstract

Abstract Anti-CD3 antibody has been used for various immune-mediated disorders through modulating immune responses. 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 as early as 3-4 hours post-administration. Furthermore, we observed that a single dose of anti-CD3 treatment was able to correct hyperglycemia in all nonobese diabetic mice with new-onset diabetes. This glucose-lowering effect was not attributable to major T cell cytokines secreted by anti-CD3 activated T cells. Furthermore, blood glucose levels of NOD-rag-/- mice lacking T cells remained unchanged after anti-CD3 treatment. 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 those of control animals. Paradoxically, the anti-CD3-treated animals were highly tolerant to the exogenous glucose challenge. In vitro studies demonstrated that anti-CD3 treatment lowered glucose levels in T cell culture media. Further studies showed that anti-CD3 antibody up-regulated GLUT-1 on activated T cells. This study indicates that anti-CD3 therapy-induced hypoglycemia is likely resulted from increased glucose consumption via enhancing glucose transportation into the activated cells induced by anti-CD3 treatment.