Journal
IMMUNITY
Volume 33, Issue 1, Pages 128-140Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2010.06.014
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Funding
- Department of Pathology
- National Institutes of Health [AI83286, AI42767, AI46653, AI50073, AI59752, AI077504, HL095540]
- Deutsche Forschungsgemeinschaft (DFG) [WI 3308/1-1]
- University of Iowa
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Repetitive antigen stimulation by prime-boost vaccination or pathogen reencounter increases memory CD8(+) T cell numbers, but the impact on memory CD8(+) T cell differentiation is unknown. Here we showed that repetitive antigen stimulations induced accumulation of memory CD8(+) T cells with uniform effector memory characteristics. However, genome-wide microarray analyses revealed that each additional antigen challenge resulted in the differential regulation of several hundred new genes in the ensuing memory CD8(+) T cell populations and, therefore, in stepwise diversification of CD8(+) T cell transcriptomes. Thus, primary and repeatedly stimulated (secondary, tertiary, and quaternary) memory CD8(+) T cells differed substantially in their molecular signature while sharing expression of a small group of genes and biological pathways, which may constitute a core signature of memory differentiation. These results reveal the complex regulation of memory CD8(+) T cell differentiation and identify potential new molecular targets to dissect the function of memory cells generated by repeated antigen stimulation.
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