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Sci. Signal., 30 September 2008
Vol. 1, Issue 39, p. ra6
[DOI: 10.1126/scisignal.1160583]

RESEARCH

Editor's Summary

ATP Signals T Cells to Activate
Sustained influx of extracellular Ca2+ is a critical event in the activation of T cells. One consequence of increased cytosolic Ca2+ concentration is the uptake of Ca2+ by mitochondria, which leads to the synthesis of adenosine triphosphate (ATP). Activation of purinergic receptors upon T cells is known to affect the outcome of stimulation of the T cell receptor (TCR), but how extracellular ATP might affect T cell function in the context of inflammation is unclear. Schenk et al. now show that on TCR triggering, ATP is released from T cells through pannexin hemichannels and functions in an autocrine fashion as a costimulator of T cell activation. Blocking ATP signaling mediated by purinergic P2X receptors on T cells in the context of TCR stimulation led to decreased T cell activation and increased expression of anergy-associated genes. Moreover, administration of a P2X receptor antagonist to mouse models of type 1 diabetes and inflammatory bowel disease substantially inhibited the development of effector T cells and lessened tissue damage compared with that in untreated mice. Together, these data suggest that therapeutic intervention against ATP synthesis and release may be of benefit in the treatment of T cell–mediated inflammatory diseases.

Citation: U. Schenk, A. M. Westendorf, E. Radaelli, A. Casati, M. Ferro, M. Fumagalli, C. Verderio, J. Buer, E. Scanziani, F. Grassi, Purinergic Control of T Cell Activation by ATP Released Through Pannexin-1 Hemichannels. Sci. Signal. 1, ra6 (2008).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Differential Regulation of P2X7 Receptor Activation by Extracellular Nicotinamide Adenine Dinucleotide and Ecto-ADP-Ribosyltransferases in Murine Macrophages and T Cells.
S. Hong, N. Schwarz, A. Brass, M. Seman, F. Haag, F. Koch-Nolte, W. P. Schilling, and G. R. Dubyak (2009)
J. Immunol. 183, 578-592
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Gap Junctions.
D. A. Goodenough and D. L. Paul (2009)
Cold Spring Harb Perspect Biol 1, a002576
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Autocrine regulation of T-cell activation by ATP release and P2X7 receptors.
L. Yip, T. Woehrle, R. Corriden, M. Hirsh, Y. Chen, Y. Inoue, V. Ferrari, P. A. Insel, and W. G. Junger (2009)
FASEB J 23, 1685-1693
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Extracellular ATP in the Immune System: More Than Just a "Danger Signal".
A. Trautmann (2009)
Science Signaling 2, pe6
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Both sides now: multiple interactions of ATP with pannexin-1 hemichannels. Focus on "A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP".
G. R. Dubyak (2009)
Am J Physiol Cell Physiol 296, C235-C241
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