Abstract
Abstract Repetitive antigen stimulation by prime-boost vaccination or pathogen re-encounter increases memory CD8 T cell numbers, however the impact on memory T cell differentiation is unknown. Here we show that repetitive antigen stimulations induce the selective accumulation of CD8 T cells with a uniform effector memory phenotype. In contrast to this, genome-wide microarray analysis reveals that each additional antigen challenge results in the differential regulation of several hundred genes in memory CD8 T cells and therefore in stepwise diversification of T cell transcriptomes. As a consequence, repeatedly stimulated memory CD8 T cells and primary memory CD8 T cells differ significantly in their molecular signature and share expression of only a small but preserved group of memory signature genes. Our results provide new insight into the complex regulation of memory CD8 T cell differentiation and identify potential new molecular targets to dissect and manipulate the function of memory T cells in human diseases.
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