Transcriptome Signatures Reveal Rapid Induction of Immune-Responsive Genes in Human Memory CD8(+) T Cells

Memory T cells (T(M)) play a prominent role in protection and auto-immunity due to their ability to mount a more effective response than naïve T cells (T(N)). However, the molecular mechanisms underlying enhanced functionality of T(M) are not well defined, particularly in human T(M). We examined the global gene expression profiles of human CD8(+) T(N) and T(M) before and after stimulation. There were 1,284, 1,373 and 1,629 differentially expressed genes between T(N) and T(M) at 0 hr, 4 hr and 24 hr after stimulation, respectively, with more genes expressed to higher levels in T(M). Genes rapidly up-regulated in T(N) cells were largely involved in nitrogen, nucleoside and amino acid metabolisms. In contrast, those in CD8(+) T(M) were significantly enriched for immune-response-associated processes, including cytokine production, lymphocyte activation and chemotaxis. Multiple cytokines were rapidly up-regulated in T(M) cells, including effector cytokines known to be produced by CD8(+) T cells and important for their functions, as well as regulatory cytokines, both pro- and anti-inflammatory, that are not typically produced by CD8(+) T cells. These results provide new insights into molecular mechanisms that contribute to the enhanced functionality of human CD8(+) T(M) and their prominent role in protection and auto-immunity.