The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.2046iti6
The Journal of Experimental Medicine, Vol. 204, No. 6, 1240b-
The Rockefeller University Press, 0022-1007 $30.00
© Bashyam
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IN THIS ISSUE

cAMP crosses junctions

Regulatory T (T reg) cells that cozy up to other T cells send inhibitory molecules through cell–cell gap junctions, according to a new study by Bopp et al. (page 1303).

Some thymus-born natural T reg cells need little more than direct contact with their T cell victims to suppress their immune functions. But the mechanism or molecule that controls this contact-dependent inhibition has not yet been found.

One known potent immune suppressor is the intracellular second messenger cyclic adenosine monophophate (cAMP), which blocks T cell proliferation. cAMP levels are low in resting T cells and only marginally increase after activation. T reg cells, however, have constantly high levels of cAMP.

The team now shows that T reg cells use their abundant cAMP to flood conventional T cells and thereby shut them down. The cAMP transfer occurred through gap junctions, which formed upon contact between a T reg cell and an activated T cell. The subsequent increase in cAMP shut down T cell proliferation. cAMP transfer into activated T cells failed when gap junction formation was disrupted.

Together with Deaglio et al. (page 1257; and see "Regulatory cells get new ID" JEM 204:1241), these studies confirm that T reg cells use cAMP and the adenosine-generating pathway to rein in immune activation. Formula



Hema Bashyam

hbashyam{at}rockefeller.edu



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Related Articles

Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression
Tobias Bopp, Christian Becker, Matthias Klein, Stefan Klein-Heßling, Alois Palmetshofer, Edgar Serfling, Valeska Heib, Marc Becker, Jan Kubach, Steffen Schmitt, Sabine Stoll, Hansjörg Schild, Martin S. Staege, Michael Stassen, Helmut Jonuleit, and Edgar Schmitt
J. Exp. Med. 2007 204: 1303-1310. [Abstract] [Full Text] [PDF]

Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression
Silvia Deaglio, Karen M. Dwyer, Wenda Gao, David Friedman, Anny Usheva, Anna Erat, Jiang-Fan Chen, Keiichii Enjyoji, Joel Linden, Mohamed Oukka, Vijay K. Kuchroo, Terry B. Strom, and Simon C. Robson
J. Exp. Med. 2007 204: 1257-1265. [Abstract] [Full Text] [PDF]




This Article
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