title: TCR-triggered extracellular superoxide production is not required for T-cell activation.
abstract: BACKGROUND
  In 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.
  
  
  RESULTS
  To 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.
  
  
  CONCLUSIONS
  Collectively, 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.
authors: Aleksey V
authors: AV
authors: Belikov
authors: Burkhart
authors: B
authors: Schraven
authors: Luca
authors: L
authors: Simeoni
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D049109:Cell Proliferation; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics; D061251:Primary Cell Culture; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D013481:Superoxides; D013482:Superoxide Dismutase; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D001205:Ascorbic Acid