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J Immunol. 2006 Oct 15;177(8):4962-5.

Cutting edge: hypoxia-inducible factor 1alpha and its activation-inducible short isoform I.1 negatively regulate functions of CD4+ and CD8+ T lymphocytes.

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  • 1New England Inflammation and Tissue Protection Institute, Northeastern University, Boston, MA 02115, USA.

Abstract

To evaluate the role of hypoxia-inducible factor 1alpha (HIF-1alpha) and its TCR activation-inducible short isoform I.1 in T cell functions, we genetically engineered unique mice with: 1) knockout of I.1 isoform of HIF-1alpha; 2) T cell-targeted HIF-1alpha knockdown; and 3) chimeric mice with HIF-1alpha gene deletion in T and B lymphocytes. In all three types of mice, the HIF-1alpha-deficient T lymphocytes, which were TCR-activated in vitro, produced more proinflammatory cytokines compared with HIF-1alpha-expressing control T cells. Surprisingly, deletion of the I.1 isoform, which represents < 30% of total HIF-1alpha mRNA in activated T cells, was sufficient to markedly enhance TCR-triggered cytokine secretion. These data suggest that HIF-1alpha not only plays a critical role in oxygen homeostasis but also may serve as a negative regulator of T cells.

PMID:
17015677
[PubMed - indexed for MEDLINE]
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