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Critical Reviews™ in Immunology

Impact factor: 3.698

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v26.i5.40
pages 443-452

Role of cAMP Phosphodiesterase 4 in Regulation of T-Cell Function

Elisa Bjorgo
The Biotechnology Centre of Oslo, University of Oslo, P.O. Box 1125 Blindern, N-0317 Oslo, Norway
Kjetil Tasken
The Biotechnology Centre of Oslo and Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Norway

ABSTRACT

Ligation of both the T-cell receptor (TCR) and the CD28 receptor is required for full T-cell activation to occur. Engagement of the TCR in primary T cells is followed by rapid cAMP production in lipid rafts resulting in raft-associated protein kinase A (PKA) activation and inhibition of proximal T-cell signaling. However, upon TCR and CD28 cross-ligation, β-arrestin in complex with cAMP-specific phosphodiesterase 4 (PDE4) is recruited to lipid rafts, thus downregulating cAMP levels. Consequently, the activities of both PKA and PDE4 seem to be important for the regulation of TCR-induced signaling and T-cell function. We, therefore, propose a novel role for TCR and CD28 co-stimulation in the downmodulation of TCR-induced cAMP-mediated inhibitory signals through the recruitment of β-arrestin and PDE4 to lipid rafts, thus allowing a full T-cell response to occur.