International Immunology Advance Access originally published online on October 18, 2004
International Immunology 2004 16(12):1711-1721; doi:10.1093/intimm/dxh172
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© 2004 The Japanese Society for Immunology
Kinetic assessment of general gene expression changes during human naive CD4+ T cell activation
1 Laboratory of Immunology, 2 Laboratory of Genetics and 3 DNA Array Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Correspondence to: N.-p. Weng; E-mail: wengn{at}grc.nia.nih.gov
The consequence of naive CD4+ T cell activation is the differentiation and generation of effector cells. How the engagement of T cell receptors and co-stimulatory receptors leads to profound differential changes is not fully understood. To assess the transcription changes during T cell activation, we developed human T cell specific cDNA microarray gene filters and examined the gene expression profiles in human naive CD4+ T cells for 10 continuous time points during the first 24 h after anti-CD3 plus anti-CD28 (anti-CD3/CD28) stimulation. We report here a global and kinetic analysis of gene expression changes during naive CD4+ T cell activation and identify 196 genes having expression levels that significantly changed after activation. Based on the temporal change, there are 15 genes that changed between 0–1 h (early), 25 genes between 2–8 h (middle) and 156 genes between 16–24 h (late) after stimulation. Further analyses of the functions of those genes indicate their roles in maintenance of resting status, activation, adhesion/migration, cell cycle progression and cytokine production. However, a significant majority of these genes are novel to T cells and their functions in T cell activation require further study. Together, these results present a kinetic view of the gene expression changes of naive CD4+ T cells in response to T cell receptor-mediated activation for the first time, and provide a basis in understanding how the complex network of gene expression regulation is programmed during CD4+ T cell activation.
Keywords: activation, cytokine, cDNA microarray, resting
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