Effects of a reduced oxygen tension culture system on human T cell clones as a function of in vitro age

Effects of hypoxia and/or lack of glucose on cellular energy metabolism and cytokine production in stimulated human CD4+ T lymphocytes

“…It has been also demonstrated years ago that neutrophils and macrophages can cope with hypoxic conditions since they are dependent more on glycolytic than on mitochondrial ATP production [10]. More recently, T cells have been found to react on hypoxia with a decreased proliferation rate [11][12][13], disturbed Ca 2+ -mediated signal transduction [14,15], as wells as with suppressed IFN-␥ secretion [16]. What is missing, however, is detailed data relating cellular energy metabolism to T cell function under impaired conditions.…”

Lifespan and oxidative stress show a non-linear response to atmospheric oxygen inDrosophila

“…Conversely, hypoxia effects on lifespan are not well studied and seem to differ between vertebrate and invertebrate models, and within cultured cells (Table1). Low oxygen tension lengthened the lifespan of human diploid fibroblasts (Chen et al, 1995), but reduced the lifespan of human CD4 and T cell clones (Duggan et al, 2004). Mice showed a lifespan reduction in hypoxia and detrimental physiological changes such as severe weight loss, trembling and polycythemia (Debonneuil et al, 2006).…”

Human Adipose-Derived Stromal/Stem Cells Induce Functional CD4+CD25+FoxP3+CD127−Regulatory T Cells Under Low Oxygen Culture Conditions

“…Toussaint et al [50] demonstrated that the observed increased T-cell proliferative response in many studies following extended culture under ambient O 2 conditions may be a skewed T-cell response. Moreover, based on the proliferation index and T-cell yield, Duggan et al [49] demonstrated that CD4/CD28 antibody-mediated T-cell proliferation was higher at ambient O 2 than at low O 2 . This was partly due to intracellular nitric oxide (NO) levels, which were skewed higher at ambient O 2 [49].…”

“…Moreover, based on the proliferation index and T-cell yield, Duggan et al [49] demonstrated that CD4/CD28 antibody-mediated T-cell proliferation was higher at ambient O 2 than at low O 2 . This was partly due to intracellular nitric oxide (NO) levels, which were skewed higher at ambient O 2 [49]. Because high levels of intracellular NO and sustained CD69 tend to downregulate T-cell responses in vivo, the lower proliferative T-cell responses in vitro under low O 2 may be considered as a reflection of in vivo regulatory mechanisms.…”

“…A low O 2 concentration (5%) is representative of O 2 levels in tissues in vivo during T-cell activation, clonal expansion, and differentiation [48][49][50]. Atkuri et al [48] demonstrated that primary T cells cultured at ambient O 2 (21%) significantly altered the intracellular redox state (stimulated production of an abnormally elevated amount of oxidized intracellular glutathione), whereas T cells cultured at an O 2 level of 5% maintained the balance of intracellular glutathione and its oxidized form that more closely resembled the in vivo status.…”