Identification of LKLF-regulated genes in quiescent CD4+ T lymphocytes.

The transcription factor LKLF (lung Krüppel-like factor) is expressed at high levels in quiescent CD4+ and CD8+ T lymphocytes and provides an important role in establishment and maintenance of the quiescent state. To identify LKLF-regulated genes, we performed microarray analysis using an established Jurkat T cell line containing a tetracycline-inducible LKLF. LKLF induction in this Jurkat T cell line generates a quiescent phenotype that resembles memory CD4+ T lymphocytes. We found that LKLF induction in Jurkat cells resulted in up-regulation (>1.5-fold) of about 100 mRNAs, while it repressed (>1.5-fold) a similar number of mRNAs. A striking feature of the LKLF-stimulated mRNAs was that a significant number of them encode cell surface proteins or proteins implicated in initiating and propagating cellular signaling cascades. The data suggests that LKLF may establish a phenotype that primes quiescent cells for responses to specific extracellular stimuli. The mRNAs encoding CDw52, IL-10R alpha and paxillin were among the most highly induced transcripts in Jurkat T cells, and we observed that the encoded proteins are down-regulated following activation of quiescent CD4+ T cells isolated from healthy blood donors. We also examined whether LKLF-induced quiescence in Jurkat cells could silence transcription of integrated HIV-1 proviruses. We found however that LKLF-induced quiescence is not sufficient to repress expression of HIV-1 proviruses in Jurkat T cells, suggesting that the HIV-1 provirus is resistant to LKLF-regulated quiescence.