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 C gamma1. 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-3beta 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.
Li
Cheng-Rui
CR
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Berg
Leslie J
LJ
D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007156:Immunologic Memory; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction
D018106:CD28 Antigens; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3