Physiological fever temperature induces a protective stress response in T lymphocytes mediated by Heat Shock Factor-1 (HSF1)

Patience Murapa, Siva Gandhapudi, Hollie S. Skaggs, Kevin D. Sarge, Jerold G. Woodward

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Heat shock factor-1 (HSF1) is a transcription factor that serves as the major temperature-inducible sensor for eukaryotic cells. In most cell types, HSF1 becomes activated to the DNA binding form at 42°C and mediates the classical heat shock response, protecting the cells from subsequent lethal temperatures. We have recently demonstrated that HSF1 is activated at a lower temperature in T lymphocytes than in most other cell types (39°C vs 42°C), within the physiological range of fever. In this study, we show that T cell activation at fever temperatures not only activates HSF1 but induces the up-regulation of the HSF1 protein and the HSF1-regulated protein, HSP70i. T cells from HSF1 knockout mice proliferate normally under optimal conditions but are impaired in proliferation at physiological fever temperatures and low CO2 concentrations, conditions that do not impair wild-type T cells. This defect in proliferation appears to be mediated by a block in the G 1/S transition of the cell cycle and is independent of HSP70. Elevated temperature and low CO2 concentrations resulted in a dramatic reduction of the intracellular reactive oxygen species (ROS) levels in both normal and knockout T cells. Wild-type T cells were able to restore ROS levels to normal within 5 h, whereas HSF1-/- T cells were not. These results suggest that the proliferation defect seen in T cells from HSF1 -/- mice at fever temperatures was because of dysregulated ROS levels and that HSF1 is important in maintaining ROS homeostasis and cell cycle progression under the stressful conditions encountered during fever.

Original languageEnglish
Pages (from-to)8305-8312
Number of pages8
JournalJournal of Immunology
Volume179
Issue number12
DOIs
StatePublished - Dec 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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