Deficiency of Small Gtpase Rac2 Affects T Cell Activation

Rac2 is a hematopoietic-specific GTPase acting as a molecular switch to mediate both transcriptional activation and cell morphological changes. We have examined the effect of Rac2 deficiency during T cell activation. In Rac2^−/− T cells, proliferation was reduced upon stimulation with either plate-bound anti-CD3 or T cell receptor–specific antigen. This defect is accompanied with decreased activation of mitogen activated protein kinase extracellular signal–regulated kinase (ERK)1/2 and p38, and reduced Ca²+ mobilization. TCR stimulation–induced actin polymerization is also reduced. In addition, anti-CD3 cross-linking–induced T cell capping is reduced compared with wild-type T cells. These results indicate that Rac2 is important in mediating both transcriptional and cytoskeletal changes during T cell activation. The phenotypic similarity of Rac2^−/− to Vav^−/− cells implicates Rac2 as a downstream mediator of Vav signaling.