Anti-CD3 Antibody Treatment Induces Hypoglycemia and Super Tolerance to Glucose Challenge in Mice through Enhancing Glucose Consumption by Activated Lymphocytes

Abstract EN

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.