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. |