Migration of Th1 Lymphocytes Is Regulated by CD152 CTLA-4-Mediated Signaling via PI3 Kinase-Dependent Akt ActivationReportar como inadecuado




Migration of Th1 Lymphocytes Is Regulated by CD152 CTLA-4-Mediated Signaling via PI3 Kinase-Dependent Akt Activation - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 CTLA-4 initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase PI3K-dependent activation of protein kinase B PKB-Akt. In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response.



Autor: Karin Knieke, Holger Lingel, Kathrin Chamaon, Monika C. Brunner-Weinzierl

Fuente: http://plos.srce.hr/



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