Persistent TNF-alpha exposure impairs store operated calcium influx in CD4+ T lymphocytes
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Colleges, School and Institutes
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.
|Number of pages||6|
|Publication status||Published - 28 Feb 2005|
- calcium (Ca2+), T-cell, T-cell receptor, tumour necrosis factor-alpha, store operated Ca2+ influx