Transcriptional insights into the CD8 + T cell response to infection and memory T cell formation

J. Adam Best, David A. Blair, Jamie Knell, Edward Yang, Viveka Mayya, Andrew Doedens, Michael L. Dustin, Ananda W. Goldrath, Paul Monach, Susan A. Shinton, Richard R. Hardy, Radu Jianu, David Koller, Jim Collins, Roi Gazit, Brian S. Garrison, Derrick J. Rossi, Kavitha Narayan, Katelyn Sylvia, Joonsoo KangAnne Fletcher, Kutlu Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon Turley, J. Adam Best, Vladimir Jojic, Daphne Koller, Tal Shay, Aviv Regev, Nadia Cohen, Patrick Brennan, Michael Brenner, Taras Kreslavsky, Natalie A. Bezman, Joseph C. Sun, Charlie C. Kim, Lewis L. Lanier, Jennifer Miller, Brian Brown, Miriam Merad, Emmanuel L. Gautier, Claudia Jakubzick, Gwendalyn J. Randolph, Francis Kim, Tata Nageswara Rao, Amy Wagers, Tracy Heng, Michio Painter, Jeffrey Ericson, Scott Davis, Ayla Ergun, Michael Mingueneau, Diane Mathis, Christophe Benoist

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)404-412
Number of pages9
JournalNature immunology
Volume14
Issue number4
DOIs
StatePublished - Apr 2013

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    Best, J. A., Blair, D. A., Knell, J., Yang, E., Mayya, V., Doedens, A., Dustin, M. L., Goldrath, A. W., Monach, P., Shinton, S. A., Hardy, R. R., Jianu, R., Koller, D., Collins, J., Gazit, R., Garrison, B. S., Rossi, D. J., Narayan, K., Sylvia, K., ... Benoist, C. (2013). Transcriptional insights into the CD8 + T cell response to infection and memory T cell formation. Nature immunology, 14(4), 404-412. https://doi.org/10.1038/ni.2536