SummaryThe accumulation of CD28 − T cells, particularly within the CD8 subset, is one of the most prominent changes during T cell homeostasis and function associated with aging in human. CD28, a major costimulatory receptor, is responsible for the optimal antigen-mediated T cell activation, proliferation, and survival of T cells. CD28 − T cells exhibit reduced antigen receptor diversity, defective antigeninduced proliferation, and a shorter replicative lifespan while showing enhanced cytotoxicity and regulatory functions. Gene expression analyses reveal profound changes of CD28 − T cells in comparison to their CD28 + counterparts and support their functional differences. Here we review the recent advance of our understanding of CD28− T cells and their role in age-associated decline of immune function.

Summary Memory lymphocytes are characterized by their ability to exhibit a rapid response to the recall antigen, in which differential transcription plays a significant role, yet the underlying mechanism is not understood. We report here a genome-wide analysis of histone methylation on two histone H3 lysine residues (H3K4me3 and H3K27me3) and gene expression profiles in naïve and memory CD8 T cells. We found that a general correlation exists between the levels of gene expression and the levels of H3K4me3 (positive correlation) and H3K27me3 (negative correlation) across the gene body. These correlations display four distinct modes: repressive, active, poised, and bivalent, reflecting different functions of these genes. Furthermore, a permissive chromatin state of each gene is established by a combination of different histone modifications. Our findings reveal a complex regulation by histone methylation in differential gene expression and suggest that histone methylation may be responsible for memory CD8 T cell function.

Generation of CD8