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

• Published in: Journal of Immunology Research Vol. 2014; no. 2014; pp. 1 - 11
• Main Authors: Wan, Suigui, Looney, Benjamin, Chernatynskaya, Anna V., Xia, Chang-Qing, Clare-Salzler, Michael J.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2014; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - immunology; Apoptosis; Autoimmune diseases; Biological Transport; Blood Glucose; C-Peptide - blood; Care and treatment; CD3 Complex - immunology; Complications and side effects; Consumption; Cytokines; Cytokines - blood; Diabetes; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - metabolism; Dosage and administration; Drug dosages; Glucose; Glucose - metabolism; Glucose Tolerance Test; Hyperglycemia; Hypoglycemia; Hypoglycemia - immunology; Hypoglycemia - metabolism; Immunologic diseases; Immunology; Inflammation Mediators - blood; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes - immunology; Lymphocytes - metabolism; Metabolism; Mice; Mice, Inbred NOD; Mice, Knockout; Peptides; Risk factors; Rodents; Viral antibodies; China
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2014/326708

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.