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Persistent TNF‐α exposure impairs store operated calcium influx in CD4+ T lymphocytes
Author(s) -
Church Leigh D.,
Goodall John E.,
Rider David A.,
Bacon Paul A.,
Young Stephen P.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.01.051
Subject(s) - t cell receptor , tumor necrosis factor alpha , thapsigargin , endocrinology , cd28 , stimulation , t cell , medicine , chemistry , receptor , cd3 , microbiology and biotechnology , calcium , immunology , biology , immune system , cd8
Persistent tumour necrosis factor alpha (TNF‐α) exposure uncouples proximal T‐cell receptor (TCR)‐signalling events. Here, we demonstrate that chronic TNF‐α exposure also attenuates signalling distal to the TCR, by specifically inhibiting Ca 2+ influx evoked by thapsigargin in CD4+ T‐cells. Mitogen‐induced Ca 2+ responses were impaired in a dose dependent manner, and TCR‐induced Ca 2+ responses were also significantly reduced. The impairment of Ca 2+ 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‐α exposure of T‐cells specifically inhibits store operated Ca 2+ influx. This may affect gene activation and contribute to the poor T‐cell function in chronic inflammatory disease.