4.7 Article

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

Journal

NATURE IMMUNOLOGY
Volume 14, Issue 4, Pages 404-412

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2536

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Funding

  1. eBioscience, Affymetrix and Expression Analysis
  2. US National Institutes of Health [AI072117, AI067545, T32 AI060536, PN2 EY016586, P30 CA016087, R24 AI072073]
  3. Pew Scholars program
  4. Cancer Research Institute

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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 TB 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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