After infection, many factors coordinate the population expansion and differentiation of CD8+ effector and memory T cells. Using data of unparalleled breadth from the Immunological Genome Project, we analyzed the CD8+ T cell transcriptome throughout infection to establish gene-expression signatures and identify putative transcriptional regulators. Notably, we found that the expression of key gene signatures can be used to predict the memory-precursor potential of CD8+ effector cells. Long-lived memory CD8+ cells ultimately expressed a small subset of genes shared by natural killer T and γδ T cells. Although distinct inflammatory milieu and T cell precursor frequencies influenced the differentiation of CD8+ effector and memory populations, core transcriptional signatures were regulated similarly, whether polyclonal or transgenic, and whether responding to bacterial or viral model pathogens. Our results provide insights into the transcriptional regulation that influence memory formation and CD8+ T cell immunity.
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We thank eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project. Supported by the US National Institutes of Health (AI072117 and AI067545 to A.W.G.; T32 AI060536 to J.A.B.; PN2 EY016586 to D.A.B. and M.L.D.; P30 CA016087 for cell sorting; and R24 AI072073 (National Institute of Allergy and Infectious Diseases) to the ImmGen Consortium), the Pew Scholars program (A.W.G.) and the Cancer Research Institute (A.W.G. and V.M.).
The authors declare no competing financial interests.
A list of members and affiliations appears at the end of the paper.
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Best, J., Blair, D., Knell, J. et al. Transcriptional insights into the CD8+ T cell response to infection and memory T cell formation. Nat Immunol 14, 404–412 (2013). https://doi.org/10.1038/ni.2536
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