Persistent TNF-alpha exposure impairs store operated calcium influx in CD4+ T lymphocytes

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

Abstract

Persistent tumour necrosis factor alpha (TNF-alpha) exposure uncouples proximal T-cell receptor (TCR)-signalling events. Here, we demonstrate that chronic TNF-alpha exposure also attenuates signalling distal to the TCR, by specifically inhibiting Ca2+ influx evoked by thapsigargin in CD4+ T-cells. Mitogen-induced Ca2+ responses were impaired in a dose dependent manner, and TCR-induced Ca2+ responses were also significantly reduced. The impairment of Ca2+ influx strongly correlated with poor function as proliferative responses to both mitogen and anti-CD3/CD28 stimulation were suppressed. Our findings show that persistent TNF-alpha exposure of T-cells specifically inhibits store operated Ca2+ influx. This may affect gene activation and contribute to the poor T-cell function in chronic inflammatory disease. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Details

Original languageEnglish
Pages (from-to)1539-1544
Number of pages6
JournalFEBS Letters
Volume579
Publication statusPublished - 28 Feb 2005

Keywords

  • calcium (Ca2+), T-cell, T-cell receptor, tumour necrosis factor-alpha, store operated Ca2+ influx