Abstract
Memory T cells (TM) play a prominent role in protection and auto-immunity due to their ability to mount a more effective response than naïve T cells (TN). However, the molecular mechanisms underlying enhanced functionality of TM are not well defined, particularly in human TM. We examined the global gene expression profiles of human CD8+ TN and TM before and after stimulation. There were 1,284, 1,373 and 1,629 differentially expressed genes between TN and TM at 0 hr, 4 hr and 24 hr after stimulation, respectively, with more genes expressed to higher levels in TM. Genes rapidly up-regulated in TN cells were largely involved in nitrogen, nucleoside and amino acid metabolisms. In contrast, those in CD8+ TM were significantly enriched for immune-response-associated processes, including cytokine production, lymphocyte activation and chemotaxis. Multiple cytokines were rapidly up-regulated in TM 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+ TM and their prominent role in protection and auto-immunity.
Highlights
While studies of gene expression in quiescent TM cells can reveal mechanisms underlying their homeostasis and maintenance, it is the genes rapidly induced after stimulation that participate in the execution of immune functions in vivo, and likely play a prominent role in contributing to the enhanced functionality of CD8+ TM cells
To uncover molecular mechanisms underlying the enhanced functionality of human CD8+ TM cells, we stimulated purified CD8+ TN (CD8+CD4−CD45RO−CD27+) and TM (CD8+CD4−CD45RO+) cells with anti-CD3/CD28 for 0, 4, and 24 hr, respectively, and measured mRNA transcripts on genome-wide microarrays
Three genes showed “opposite” changes, which were up-regulated in TM cells while down-regulated in TN cells, or contrarily, fourteen genes were up-regulated in TN cells while down-regulated in TM cells
Summary
CD8+ TM cells display the unique property of rapid recall responses, characterized by immediate effector cytokine production and rapid proliferation upon antigen re-encounter[1,3,4,5] These characteristics of CD8+ TM cells have been mostly defined in murine infection models, where infection can be controlled and antigen-specific T cells can be tracked by using TCR-transgenic cells[6,7,8,9]. While studies of gene expression in quiescent TM cells can reveal mechanisms underlying their homeostasis and maintenance, it is the genes rapidly induced after stimulation that participate in the execution of immune functions in vivo, and likely play a prominent role in contributing to the enhanced functionality of CD8+ TM cells. Our results provide new insights into the enhanced functionality of human CD8+ TM cells
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