title: T cell adhesion primes antigen receptor-induced calcium responses through a transient rise in adenosine 3',5'-cyclic monophosphate.
abstract: 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.
authors.affiliation: Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, UMR 8104, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Conche
authors.forename: Geneviève
authors.initials: G
authors.lastname: Boulla
authors.forename: Alain
authors.initials: A
authors.lastname: Trautmann
authors.forename: Clotilde
authors.initials: C
authors.lastname: Randriamampita
mesh_terms: 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
chemical_list: D011946:Receptors, Antigen; D011948:Receptors, Antigen, T-Cell; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium