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Anti-CD3 Antibody Treatment Induces Hypoglycemia and Super Tolerance to Glucose Challenge in Mice through Enhancing Glucose Consumption by Activated Lymphocytes
- Source :
- Journal of Immunology Research, Vol 2014 (2014), Journal of Immunology Research
- Publication Year :
- 2014
- Publisher :
- Hindawi Limited, 2014.
-
Abstract
- 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 cellsin vitroandin 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.
- Subjects :
- Blood Glucose
lcsh:Immunologic diseases. Allergy
medicine.medical_specialty
CD3 Complex
Article Subject
T cell
Immunology
Spleen
Hypoglycemia
Lymphocyte Activation
Diabetes Mellitus, Experimental
Mice
In vivo
Mice, Inbred NOD
Internal medicine
Diabetes mellitus
medicine
Immunology and Allergy
Animals
Lymphocytes
Mice, Knockout
biology
C-Peptide
Deoxyglucose
Antibodies, Monoclonal
Biological Transport
General Medicine
Glucose Tolerance Test
medicine.disease
medicine.anatomical_structure
Endocrinology
Glucose
biology.protein
Cytokines
GLUT1
Antibody
Inflammation Mediators
lcsh:RC581-607
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 23147156 and 23148861
- Volume :
- 2014
- Database :
- OpenAIRE
- Journal :
- Journal of Immunology Research
- Accession number :
- edsair.doi.dedup.....40211bcd5b046a6cdc0e22b16076d079