Regulation of innate CD8 + T-cell activation mediated by cytokines

Bailey E. Freeman, Erika Hammarlund, Hans Peter Raué, Mark K. Slifka

Research output: Contribution to journalArticlepeer-review

138 Scopus citations


Virus-specific CD8 + T cells develop the ability to function in an "innate" capacity by responding to a remarkable array of cytokines in a TCR-independent manner. Although several cytokines such as IL-12 and IL-18 have been identified as key regulators of CD8 + T-cell activation, the role of other cytokines and the ways in which they interact with each other remain unclear. Here, we have used an unbiased, systematic approach to examine the effects of 1,849 cytokine combinations on virus-specific CD8 + T-cell activation. This study identifies several unexpected cytokine combinations that synergize to induce antigen-independent IFNγproduction and CD69 up-regulation by CD8 + T cells in addition to cytokines that exhibit differential regulatory functions, with the ability to either enhance or inhibit T-cell IFNγ production, depending on which cytokine partner is present. These findings underscore the complexity of cytokine interactions while also providing insight into the multifaceted regulatory network controlling virus-specific CD8 + T-cell functions.

Original languageEnglish (US)
Pages (from-to)9971-9976
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - Jun 19 2012
Externally publishedYes


  • Interleukin
  • Lymphocyte
  • Lymphocytic choriomeningitis virus
  • Mouse

ASJC Scopus subject areas

  • General


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