Kinetic assessment of general gene expression changes during human naive CD4+ T cell activation.
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.
Hess
Krista
K
Laboratory of Immunology, National Institutes on Aging, National Institute of Health, Baltimore, MD 21224, USA.
Yang
Yinhua
Y
Golech
Susanne
S
Sharov
Alexei
A
Becker
Kevin G
KG
Weng
Nan-Ping
NP
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation / Q000235:genetics* / Q000502:physiology; D016853:Muromonab-CD3 / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D016853:Muromonab-CD3; D011948:Receptors, Antigen, T-Cell