It is now generally accepted that CD28 is an important costimulator for the TCR/CD3 complex promoting a sustained signaling cascade that will allow the T cell to proliferate and function. Using Ab-coated surfaces the authors show, that CD28 engagement induce the formation of cytoplasmic elongations enriched in filamentous actin (microspikes). Small Rho GTPases, namely Cdc42, Rac, and Rho, have been associated with remodelling of the actin cytoskeleton in many cell types, including T lymphocytes. To further reveal the role of Cdc42, primary human T cells were nucleofected with expression vectors encoding a GFP fusion protein of either a dominant-negative (DN) version, or a constitutively active (CA) version of Cdc42. Cells were plated on coverslips coated with CD28 or PLL and stained for F-actin. Immunofluorescence images show that Cdc42 is responsible of CD28-induced actin reorganization and the formation of microspikes.