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Autocrine regulation of T‐cell activation by ATP release and P2X 7 receptors
Author(s) -
Yip Linda,
Woehrle Tobias,
Corriden Ross,
Hirsh Mark,
Chen Yu,
Inoue Yoshiaki,
Ferrari Vhe,
Insel Paul A.,
Junger Wolfgang G.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-126458
Subject(s) - receptor , microbiology and biotechnology , purinergic receptor , autocrine signalling , apyrase , nfat , jurkat cells , extracellular , t cell receptor , chemistry , biology , t cell , biochemistry , immunology , transcription factor , immune system , gene
T‐cell activation requires the influx of extracellular calcium, although mechanistic details regarding such activation are not fully defined. Here, we show that P2X 7 receptors play a key role in calcium influx and downstream signaling events associated with the activation of T cells. By real‐time PCR and immu‐nohistochemistry, we find that Jurkat T cells and human CD4 + T cells express abundant P2X 7 receptors. We show, using a novel fluorescent microscopy technique, that T‐cell receptor (TCR) stimulation triggers the rapid release of ATP (<100 μM). This release of ATP is required for TCR‐mediated calcium influx, NFAT activation, and interleukin‐2 (IL‐2) production. TCR activation up‐regulates P2X 7 receptor gene expression. Removal of extracellular ATP by apyrase or alkaline phosphatase treatment, inhibition of ATP release with the maxi‐anion channel blocker gadolinium chloride, or siRNA silencing of P2X 7 receptors blocks calcium entry and inhibits T‐cell activation. Moreover, lymphocyte activation is impaired in C57BL/6 mice that express poorly functional P2X 7 receptors, compared to control BALB/c mice, which express fully functional P2X 7 receptors. We conclude that ATP release and autocrine, positive feedback through P2X 7 receptors is required for the effective activation of T cells.—Yip, L., Woe–hrle, T.,Corriden, R., Hirsh, M., Chen, Y., Inoue, Y., Ferrari, V., Insel, P.A., Junger, W.G. Autocrine regulation of T‐cell activation by ATP release and P2X7 receptors. FASEBJ. 23, 1685–1693 (2009)