title: Anti-CD3 antibody treatment induces hypoglycemia and super tolerance to glucose challenge in mice through enhancing glucose consumption by activated lymphocytes.
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 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.
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China ; Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Chang-Qing
authors.identifier: 0000-0002-3832-1091
authors.initials: CQ
authors.lastname: Xia
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Chernatynskaya
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Looney
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.
authors.forename: Suigui
authors.initials: S
authors.lastname: Wan
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clare-Salzler
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D001692:Biological Transport; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D017252:CD3 Complex / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007003:Hypoglycemia / Q000276:immunology* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout
chemical_list: D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D002096:C-Peptide; D017252:CD3 Complex; D016207:Cytokines; D018836:Inflammation Mediators; D005947:Glucose
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