Comparative microarray analysis of gene expression during activation of human peripheral blood T cells and leukemic...

Activation of T cells involves a complex cascade of signal transduction pathways linking T-cell receptor engagement at the cell membrane to the transcription of multiple genes within the nucleus. The T-cell leukemia-derived cell line Jurkat has generally been used as a model system for the activation of T cells. However, genome-wide comprehensive studies investigating the activation status, and thus the appropriateness, of this cell line for this purpose have not been performed. We sought to compare the transcriptional profiles of phenotypically purified human CD2(+) T cells with those of Jurkat T cells during T-cell activation, using cDNA microarrays containing 6912 genes. About 300 genes were up-regulated by more than 2-fold during activation of both peripheral blood (PB) T cells and Jurkat T cells. The number of down-regulated genes was significantly lower than that of up-regulated genes. Only 79 genes in PB T cells and 37 genes in Jurkat T cells were down-regulated by more than 2-fold during activation. Comparison of gene expression during activation of Jurkat and PB T cells revealed a common set of genes that were up-regulated, such as Rho GTPase-activating protein 1, SKP2, CDC25A, T-cell specific transcription factor 7, cytoskeletal proteins, and signaling molecules. Genes that were commonly down-regulated in both PB T cells and Jurkat T cells included CDK inhibitors (p16, p19, p27), proapoptotic caspases, and the transcription factors c-fos and jun-B. After activation, 71 genes in PB T cells and only 3 genes in Jurkat T cells were up-regulated 4-fold or more. Of these up-regulated genes and expressed sequence tags, 44 were constitutively expressed at high levels in nonactivated Jurkat cells. Quantitative real-time RT-PCR analysis confirmed our microarray data. Our findings indicate that although there is significant overlap in the activation-associated transcriptional profiles in PB T cells compared with Jurkat T cells, there is a subset of genes showing differential expression patterns during the activation of the two cell types.