T-cell activation under hypoxic conditions enhances IFN-γ secretion

Jessica Roman, Tirumalai Rangasamy, Jia Guo, Siva Sugunan, Nida Meednu, Gopinath Packirisamy, Larissa A. Shimoda, Amit Golding, Gregg Semenza, Steve N. Georas

Research output: Contribution to journalArticlepeer-review

Abstract

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% O2) and hypoxic (1% O2) conditions. Here we report that stimulation under hypoxic conditions augments the secretion of effector CD4+ T-cell cytokines, especially IFN-γ. The enhancing effects of hypoxia on IFN-γ 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-1α. Using T cells from IFN-γ receptor-deficient mice and promoter reporter studies in transiently transfected Jurkat T cells, we found that the enhancing effects of hypoxia on IFN-γ expression were not due to effects on IFN-γ 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-γ secretion and other cytokines. We conclude that hypoxia is a previously underappreciated modulator of effector cytokine secretion in CD4 + T cells.

Original languageEnglish (US)
Pages (from-to)123-128
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume42
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • CD4 T cells
  • Effector cytokine
  • Gene regulation
  • Hypoxia
  • IFN-γ

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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