Anti-CD3 Antibody Treatment Induces Hypoglycemia and Super Tolerance to Glucose Challenge in Mice through Enhancing Glucose Consumption by Activated Lymphocytes
机构:[1]Department of Hematology, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China血液科首都医科大学宣武医院[2]Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA
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.
基金:
National Natural Science Foundation of China (81172854 and 81240015)
Florida State Lung Transplantation Program
第一作者机构:[1]Department of Hematology, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China[2]Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA
通讯作者:
通讯机构:[1]Department of Hematology, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China[2]Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA
推荐引用方式(GB/T 7714):
Chang-Qing Xia,Anna V. Chernatynskaya,Benjamin Looney,et al.Anti-CD3 Antibody Treatment Induces Hypoglycemia and Super Tolerance to Glucose Challenge in Mice through Enhancing Glucose Consumption by Activated Lymphocytes[J].JOURNAL OF IMMUNOLOGY RESEARCH.2014,2014:doi:10.1155/2014/326708.
APA:
Chang-Qing Xia,Anna V. Chernatynskaya,Benjamin Looney,Suigui Wan&Michael J. Clare-Salzler.(2014).Anti-CD3 Antibody Treatment Induces Hypoglycemia and Super Tolerance to Glucose Challenge in Mice through Enhancing Glucose Consumption by Activated Lymphocytes.JOURNAL OF IMMUNOLOGY RESEARCH,2014,
MLA:
Chang-Qing Xia,et al."Anti-CD3 Antibody Treatment Induces Hypoglycemia and Super Tolerance to Glucose Challenge in Mice through Enhancing Glucose Consumption by Activated Lymphocytes".JOURNAL OF IMMUNOLOGY RESEARCH 2014.(2014)