Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression
The Journal of experimental medicine. Bd. 204. H. 6. New York, NY: Rockefeller Univ. Press 2007 S. 1303 - 1310
Erscheinungsjahr: 2007
ISBN/ISSN: 0022-1007
Publikationstyp: Zeitschriftenaufsatz (Forschungsbericht)
Sprache: Englisch
Doi/URN: 10.1084/jem.20062129
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Inhaltszusammenfassung
Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset of T cells, which are crucial for the maintenance of peripheral tolerance by controlling potentially autoreactive T cells. However, the underlying molecular mechanisms of this strictly cell contact-dependent process are still elusive. Here we show that naturally occurring T reg cells harbor high levels of cyclic adenosine monophosphate (cAMP). This second messenger is known to be a potent inhibitor of proliferati...Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset of T cells, which are crucial for the maintenance of peripheral tolerance by controlling potentially autoreactive T cells. However, the underlying molecular mechanisms of this strictly cell contact-dependent process are still elusive. Here we show that naturally occurring T reg cells harbor high levels of cyclic adenosine monophosphate (cAMP). This second messenger is known to be a potent inhibitor of proliferation and interleukin 2 synthesis in T cells. Upon coactivation with naturally occurring T reg cells the cAMP content of responder T cells is also strongly increased. Furthermore, we demonstrate that naturally occurring T reg cells and conventional T cells communicate via cell contact-dependent gap junction formation. The suppressive activity of naturally occurring T reg cells is abolished by a cAMP antagonist as well as by a gap junction inhibitor, which blocks the cell contact-dependent transfer of cAMP to responder T cells. Accordingly, our results suggest that cAMP is crucial for naturally occurring T reg cell-mediated suppression and traverses membranes via gap junctions. Hence, naturally occurring T reg cells unexpectedly may control the immune regulatory network by a well-known mechanism based on the intercellular transport of cAMP via gap junctions.» weiterlesen» einklappen
Autoren
Klassifikation
DFG Fachgebiet:
2.21 - Mikrobiologie, Virologie und Immunologie
DDC Sachgruppe:
Medizin
