Memory T cells derived from nave T cells after antigenic stimulation are able to mount a more rapid and robust recall immune response than the primary response. Differential gene expression provides a transcriptional basis of the rapid and robust memory T cell functions. However, the molecular basis of the differential gene expression was not fully understood. Here, we study human nave and memory CD8 T cells by identification of differentially expressed genes and characterization of histone modifications associated open (H3K9ac and H3K4me3) and close (H3K27me3) chromatin state in the loci of these genes. We found that gene expressions were positively correlated with the levels of H3K9ac and H3K4me3 and negatively correlated with the levels of H3K27me3 in these gene loci in resting and activated CD8 nave and memory T cells. We further identified four modes of the relationship of histone methylation and gene expression, i.e. repressive, active, poise, and bivalent. Together, these findings suggest that chromatin states mediated by histone modifications serves as a fundamental basis for the rapid and robust transcriptional response in memory CD8 T cells. Currently, we are analyzing the kinetic changes of histone modifications during CD8 T cell activation and role of histone modifying enzyme in memory CD8 T cell function. Chemokines play a pivotal role in regulating T cell function and migration in a space and time tight fashion. Here we show the role of microRNA 125b (miR-125b) in the regulation of CCL4 expression in CD8 T cells. CCL4 expression level was very low but detectable in resting nave and highly induced after in vitro activation. We found that the levels of miR-125b expression displayed a strong inverse correlation to the levels of CCL4 in resting and activated nave CD8 T cells. Furthermore, we found a reciprocal change of miR-125b and CCL4 in resting nave CD8 T cells with age. We then demonstrated that miR-125b recognized a seed sequence in the 3 UTR region of CCL4 and down-regulated CCL4 expression. Finally, we showed that changing miR-125b expression levels result in an inverse change of CCL4 expression in nave CD8 T cells. Our study unveils a molecular link between CCL4 and miR-125b in nave CD8 T cells and their alteration during aging. Diminished expression of miR-125b is at least partially responsible for the increase in CCL4 expression in nave CD8 T cells in aging, providing a potential therapeutic target for reducing the inflammatory state in the elderly.
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