T cell adhesion primes antigen receptor-induced calcium responses through a transient rise in adenosine 3',5'-cyclic monophosphate.
It is well established that sustained increases in cyclic AMP (cAMP) such as those triggered by forskolin inhibit T cell activation. We describe here an unexpected phenomenon: in T cells, a transient cAMP increase triggered by the interaction with a dendritic cell strongly potentiates T cell receptor (TCR) signaling. We discovered this effect by examining the molecular basis of the adhesion-dependent sensitization of T cells. T cell adhesion caused extracellular-signal-regulated kinase (ERK) activation, which was necessary for the sensitization process. T cell sensitization could be mimicked in suspended cells by the uncaging of caged cAMP upon ultraviolet illumination. Calcium responses occurring in T cells upon interaction with dendritic cells were strongly inhibited when protein kinase A activation was blocked. Thus, whereas sustained cAMP increases are well known to inhibit TCR signaling, transient cAMP increases occurring physiologically upon formation of an immunological synapse facilitate antigen detection.
Conche
Claire
C
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, UMR 8104, Paris, France.
Boulla
Geneviève
G
Trautmann
Alain
A
Randriamampita
Clotilde
C
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D011946:Receptors, Antigen / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D011946:Receptors, Antigen; D011948:Receptors, Antigen, T-Cell; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium