| First Author | Roman J | Year | 2010 |
| Journal | Am J Respir Cell Mol Biol | Volume | 42 |
| Issue | 1 | Pages | 123-8 |
| PubMed ID | 19372249 | Mgi Jnum | J:168451 |
| Mgi Id | MGI:4888215 | Doi | 10.1165/rcmb.2008-0139OC |
| Citation | Roman J, et al. (2010) T-cell activation under hypoxic conditions enhances IFN-gamma secretion. Am J Respir Cell Mol Biol 42(1):123-8 |
| abstractText | Secondary lymphoid organs and peripheral tissues are characterized by hypoxic microenvironments, both in the steady state and during inflammation. Although hypoxia regulates T-cell metabolism and survival, very little is known about whether or how hypoxia influences T-cell activation. We stimulated mouse CD4(+) T cells in vitro with antibodies directed against the T-cell receptor (CD3) and CD28 under normoxic (20% O(2)) and hypoxic (1% O(2)) conditions. Here we report that stimulation under hypoxic conditions augments the secretion of effector CD4(+) T-cell cytokines, especially IFN-gamma. The enhancing effects of hypoxia on IFN-gamma secretion were independent of mouse strain, and were also unaffected using CD4(+) T cells from mice lacking one copy of the gene encoding hypoxia-inducible factor-1alpha. Using T cells from IFN-gamma receptor-deficient mice and promoter reporter studies in transiently transfected Jurkat T cells, we found that the enhancing effects of hypoxia on IFN-gamma expression were not due to effects on IFN-gamma consumption or proximal promoter activity. In contrast, deletion of the transcription factor, nuclear erythroid 2 p45-related factor 2 attenuated the enhancing effect of hypoxia on IFN-gamma secretion and other cytokines. We conclude that hypoxia is a previously underappreciated modulator of effector cytokine secretion in CD4(+) T cells. |
