Antigen recognition by the T cell receptor and costimulatory signal through CD28 receptor are required for a complete T-cell activation. CD28 ligation regulates a wide range of biochemical processes that drive T-cell proliferation, prevent apoptosis and enhance IL-2 production. However, the direct effect of CD28 signaling on the global gene transcription after T-cell activation remains controversial. We described the transcriptional profile of CD28 costimulation employing microarray analysis of human naïve CD4+ T cells. Although we demonstrated that CD28-dependent signaling had quantitative effects on gene expression during the first stages of activation, strong qualitative changes on transcription were observed by 24 hours after activation. Among the genes directly induced by CD28 costimulation we identified the transcription factor Dec1. We described the critical role of Dec1 for the transcriptional response to CD28 costimulation in both Jurkat T cells and primary mouse CD4+ T cells. Importantly, we showed that the effects of Dec1 deficiency impact specifically on CD28 costimulation-dependent gene expression. Further, we proved that Dec1 is necessary to induce experimental autoimmune encephalitis in mice after MOG peptide immunization. This observation validates the in vivo importance of Dec1 for immune system function in a CD28-dependent disease.
- Copyright © 2011 by The American Association of Immunologists, Inc.