TCR-triggered extracellular superoxide production is not required for T-cell activation

Cell Communication and Signaling

Research

Luca Simeoni¹  Aleksey V Belikov¹  Burkhart Schraven² 

[1] Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany;Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany;Department of Immune Control, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Braunschweig, Germany;

关键词: Reactive oxygen species;    ROS;    T lymphocyte;    T-cell receptor;    Proliferation;    Cytokine profile;    NADPH oxidase;    NOX2;    gp91phox−/−;    Antioxidants;   

DOI  :  10.1186/s12964-014-0050-1

 received in 2014-02-10, accepted in 2014-07-21,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundIn the last decade, reactive oxygen species (ROS) production has been shown to occur upon T-cell receptor (TCR) stimulation and to affect TCR-mediated signalling. However, the exact reactive species that are produced, how ROS are generated and their requirement for T-cell activation, proliferation or cytokine production remain unclear, especially in the case of primary human T cells. Moreover, several groups have questioned that ROS are produced upon TCR stimulation.ResultsTo shed some light onto this issue, we specifically measured superoxide production upon TCR ligation in primary human and mouse T lymphocytes. We showed that superoxide is indeed produced and released into the extracellular space. Antioxidants, such as superoxide dismutase and ascorbate, abolished superoxide production, but surprisingly did not affect activation, proliferation and cytokine secretion in TCR-stimulated primary human T cells. It has been suggested that T cells produce ROS via the NADPH oxidase 2 (NOX2). Therefore, we investigated whether T-cell activation is affected in NOX2-deficient mice (gp91phox −/−). We found that T cells from these mice completely lack inducible superoxide production but display normal upregulation of activation markers and proliferation.ConclusionsCollectively, our data indicate that primary T cells produce extracellular superoxide upon TCR triggering, potentially via NOX2 at the plasma membrane. However, superoxide is not required for T-cell activation, proliferation and cytokine production.

【 授权许可】

CC BY   
© Belikov et al.; licensee BioMed Central Ltd 2014