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.