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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.

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.

SUBMITTER: Xia CQ

PROVIDER: S-EPMC3987876 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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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.

Xia Chang-Qing CQ Chernatynskaya Anna V AV Looney Benjamin B Wan Suigui S Clare-Salzler Michael J MJ

Journal of immunology research 20140211

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 dia ...[more]

PMID: 24741590

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Project description:BackgroundChronic persistent infections have been associated with T lymphocytes functional impairment. The aim of this study was to compare the activation status, the proliferative potential and the expression of CD28 and CD3? chain on T lymphocytes between chronic chagasic patients and uninfected controls.Methodology/principal findingsForty-two chronic chagasic patients, 28 healthy individuals and 32 non-chagasic cardiomyopathy donors were included. Peripheral blood was marked for CD3, CD4, CD8, HLA-DR, CD28, CD38 and intracellular CD3?. Peripheral blood mononuclear cells were stained with carboxyfluorescein diacetate succinimidylester and incubated with T. cruzi lysate or phytohemagglutinin for five days. Cells from 3 healthy controls were incubated with T. cruzi trypomastigotes separated with transwells; and the expression of CD3? chain and proliferation index was determined. Heart-infiltrating cells from two chronic chagasic patients were tested for the aforementioned cellular markers. Chagasic patients displayed higher frequencies of CD4+/HLA-DR+/CD38+ (8.1% ± 6.1) and CD8+/HLA-DR+/CD38+ (19.8 ± 8.9) T cells in comparison with healthy (1.6 ± 1.0; 10.6 ± 8.0) and non-chagasic cardiomyopathy donors (2.9 ± 2.9; 5.8 ± 6.8). Furthermore, the percentage of CD4+ activated T cells was higher in chagasic patients with cardiac involvement. CD8+ T cells proliferation index in chagasic donors (1.7 ± 0.3) was lower when compared with healthy (2.3 ± 0.3) and non-chagasic cardiomyopathy individuals (3.1 ± 1.1). The frequencies of CD4+/CD28+ and CD8+/CD28+ T cells, as well as the CD3?(bright)/CD3?(dim)% ratios in CD4+ and CD8+ were lower in chagasic patients when compared with both control groups. The CD3?(bright)/CD3?(dim)% ratio and proliferative indexes for CD4+ and CD8+ T lymphocytes decreased gradually in those cells cultivated with parasites and displayed lower values than those incubated with medium alone. Finally, heart-infiltrating T cells from two T. cruzi infected patients also expressed activation markers and down-regulate CD28 and CD3?.ConclusionsCD8+ T lymphocytes from chagasic donors displayed reduced proliferative capacity, which might be associated with CD3? down-regulation and diminished CD28 expression on CD4 T cells.

Project description:BackgroundAlthough intake of Hass avocado has been cross-sectionally linked to lower abdominal obesity, knowledge of the effects of avocado consumption on abdominal adiposity and glycemic outcomes remains limited.ObjectiveThe effects of avocado consumption on abdominal adiposity, insulin resistance, oral-glucose-tolerance test (OGTT), and estimated β-cell function were evaluated.MethodsA total of 105 adults aged 25-45 y (61% female) with BMI ≥25 kg/m2 were randomly assigned to an intervention (N = 53) that received a daily meal with 1 fresh Hass avocado or a control (N = 52) that received an isocaloric meal with similar ingredients without avocado for 12 wk. DXA was used to assess the primary outcomes of abdominal adiposity [visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and the ratio of VAT to SAAT (VS Ratio)]. Fasted glucose and insulin were used to assess the primary outcomes of insulin resistance (HOMA-IR), and insulin sensitivity (Matsuda index) and β-cell function (Insulinogenic index) were estimated using an OGTT. Changes between groups were compared using an ANCOVA. Secondary analyses were conducted based on sex.ResultsThe control group exhibited a greater reduction in SAAT [-54.5 ± 155.8 g (control) compared with 17.4 ± 155.1 g (treatment), P = 0.017] and increase in VS Ratio [0.007 ± 0.047 (control) compared with -0.011 ± 0.044 (treatment), P = 0.024]. Among females, the treatment group exhibited a greater reduction in VAT [1.6 ± 89.8 g (control) compared with -32.9 ± 81.6 g (treatment), P = 0.021] and VS Ratio [0.01 ± 0.05 (control) compared with -0.01 ± 0.03 (treatment), P = 0.001]. Among males, there was no significant difference between groups in changes in abdominal adiposity or glycemic outcomes.ConclusionsDaily consumption of 1 fresh Hass avocado changed abdominal adiposity distribution among females but did not facilitate improvements in peripheral insulin sensitivity or β-cell function among adults with overweight and obesity.This study was registered at clinicaltrials.gov as NCT02740439.

Dataset Information

Anti-CD3 antibody treatment induces hypoglycemia and super tolerance to glucose challenge in mice through enhancing glucose consumption by activated lymphocytes.

Publications

Anti-CD3 antibody treatment induces hypoglycemia and super tolerance to glucose challenge in mice through enhancing glucose consumption by activated lymphocytes.

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