Cutting Edge: Itk Is Not Essential for CD28 Signaling in Naive T Cells

Itk, a member of the Tec family of tyrosine kinases, is critical for TCR signaling, leading to the activation of phospholipase Cγ1. Early biochemical studies performed in tumor cell lines also implicated Itk in CD28 signaling. These data were complemented by functional studies on primary Itk−/− T cells that suggested a negative role for Itk in CD28 signaling. In this report, we describe a thorough analysis of CD28-mediated responses in T cells lacking Itk. Using purified naive CD4+ T cells from Itk−/− mice, we examine a range of responses dependent on CD28 costimulation. We also analyze Akt and glycogen synthase kinase-3β phosphorylation in response to stimulation of CD28 alone. Overall, these experiments demonstrate that CD28 signaling, as well as CD28-mediated costimulation of TCR signaling, function efficiently in the absence of Itk. These findings indicate that Itk is not essential for CD28 signaling in primary naive CD4+ T cells.