Gene expression and generation of CD28−CD8 T cells mediated by interleukin 15

Accumulation of CD28−CD8 T cells that are defective in response to antigenic stimulation is a hallmark of age-associated decline in T cell function. However, the underlying mechanism of this age-associated change is not fully understood. We recently analyzed the global gene expression profiles of CD8 T cell subsets from naı¨ve to memory (CD28+ to CD28−) cells and the growth of CD28+ and CD28−CD8 memory T cells in response to homeostatic cytokine interleukin 15 (IL-15). At the gene expression level, one of the most striking changes is the altered expression of some co-stimulatory receptors and various NK cell receptors in CD28−CD8 T cells. Furthermore, CD28−CD8 T cells appear to have a normal proliferation response to IL-15 in vitro. Interestingly, IL-15 is also capable of inducing stable loss of CD28 expression in actively dividing CD28+CD8 memory T cells. Together, these findings provide the gene expression features of CD28−CD8 T cells that differ from their CD28+ counterparts and suggest a possible role of IL-15 in the increase of CD28−CD8 T cells that occurs with aging.