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Publication : An adenoviral vector encoding dominant negative Cbl lowers the threshold for T cell activation in post-thymic T cells.

First Author  Zha Y Year  2007
Journal  Cell Immunol Volume  247
Issue  2 Pages  95-102
PubMed ID  17897636 Mgi Jnum  J:126344
Mgi Id  MGI:3761054 Doi  10.1016/j.cellimm.2007.07.006
Citation  Zha Y, et al. (2007) An adenoviral vector encoding dominant negative Cbl lowers the threshold for T cell activation in post-thymic T cells. Cell Immunol 247(2):95-102
abstractText  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.
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