کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2168015 | 1092369 | 2007 | 8 صفحه PDF | دانلود رایگان |
Cbl family ubiquitin ligases act as key negative regulators of TCR signaling. Knockout mice lacking Cbl-b and c-Cbl show augmented T cell activation and CD28-independent IL-2 production. In order to study Cbl function directly in post-thymic T cells, a DN Cbl adenovirus was generated for transduction of T cells from Coxsackie/adenovirus receptor (CAR) transgenic (Tg) mice. We show that dominant negative (DN) Cbl-transduced CD4+ T cells exhibited enhanced IL-2 production upon TCR/CD28 engagement compared with empty adenoviral vector-transduced cells. This augmentation was reflected at both IL-2 mRNA and protein level, and correlated with increased protein phosphorylation of Vav, Akt, ERK, and p38MAPK. Our results indicate that introduction of dominant negative Cbl can potentiate activation of post-thymic CD4+ T cells, which argues for development of strategies to interfere with Cbl function as a method of immunopotentiation.
Journal: Cellular Immunology - Volume 247, Issue 2, June 2007, Pages 95–102