Block of T lymphocyte differentiation by activation of the cAMP-dependent signal transduction pathway. |
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| Authors: | E Lalli P Sassone-Corsi R Ceredig |
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| Affiliation: | Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP, Strasburg, France. |
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| Abstract: | ![]()
Differentiation of T lymphocytes is a complex and finely tuned process. Here we show that treatment of mouse fetal thymus organ cultures with agents activating the cAMP-dependent signalling pathway results in the block of thymocyte differentiation. This is due to severe impairment of maturation beyond the CD4-/CD8- stage. In addition, rearrangements at the TCR alpha gene locus, but not at the TCR beta locus, are completely inhibited. The cAMP effect is reversible and is restricted to TCR alpha beta+ cells. cAMP acts both by triggering apoptosis and by inducing cell-cycle block in thymocytes. Thus, activation of the cAMP pathway provides a mechanism to modulate thymic function for hormones and ligands whose receptors are coupled to adenylate cyclase. |
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