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

RESEARCH ARTICLES

Purinergic Control of T Cell Activation by ATP Released Through Pannexin-1 Hemichannels

Ursula Schenk1, Astrid M. Westendorf2, Enrico Radaelli3, Anna Casati1,4, Micol Ferro1, Marta Fumagalli5, Claudia Verderio6, Jan Buer2, Eugenio Scanziani3, and Fabio Grassi1*

1 Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
2 Institute of Medical Microbiology, University Hospital Essen, 45122 Essen, Germany.
3 Department of Veterinary Pathology, Hygiene and Public Health, University of Milan, 20100 Milan, Italy.
4 Department of Biology and Genetics for Medical Sciences, University of Milan, 20100 Milan, Italy.
5 Department of Pharmacological Sciences, University of Milan, 20100 Milan, Italy.
6 Department of Medical Pharmacology, CNR Institute of Neuroscience, University of Milan, 20100 Milan, Italy.

Abstract: T cell receptor (TCR) stimulation results in the influx of Ca2+, which is buffered by mitochondria and promotes adenosine triphosphate (ATP) synthesis. We found that ATP released from activated T cells through pannexin-1 hemichannels activated purinergic P2X receptors (P2XRs) to sustain mitogen-activated protein kinase (MAPK) signaling. P2XR antagonists, such as oxidized ATP (oATP), blunted MAPK activation in stimulated T cells, but did not affect the nuclear translocation of the transcription factor nuclear factor of activated T cells, thus promoting T cell anergy. In vivo administration of oATP blocked the onset of diabetes mediated by anti-islet TCR transgenic T cells and impaired the development of colitogenic T cells in inflammatory bowel disease. Thus, pharmacological inhibition of ATP release and signaling could be beneficial in treating T cell–mediated inflammatory diseases.

* To whom correspondence should be addressed. E-mail: fabio.grassi{at}irb.unisi.ch

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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