Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin Academic Article uri icon


MeSH Major

  • Arenaviridae Infections
  • CD8-Positive T-Lymphocytes
  • Interleukin-17
  • Lymphocytic choriomeningitis virus
  • T-Box Domain Proteins


  • When intracellular pathogens invade mammalian hosts, na├»ve CD8+ T cells differentiate into cytotoxic killers, which lyse infected target cells and secrete cytokines that activate intracellular microbicides. We show that CD8+ T cells deficient in the transcription factors T-bet and eomesodermin (Eomes) fail to differentiate into functional killers required for defense against lymphocytic choriomeningitis virus. Instead, virus-specific CD8+ T cells lacking both T-bet and Eomes differentiate into an interleukin-17-secreting lineage, reminiscent of the helper T cell fate that has been implicated in autoimmunity and extracellular microbial defense. Upon viral infection, mice with T cells lacking both T-bet and Eomes develop a CD8+ T cell-dependent, progressive inflammatory and wasting syndrome characterized by multi-organ infiltration of neutrophils. T-bet and Eomes, thus, ensure that CD8+ T cells adopt an appropriate course of intracellular rather than extracellular destruction.

publication date

  • July 18, 2008



  • Academic Article



  • eng

PubMed Central ID

  • PMC2807624

Digital Object Identifier (DOI)

  • 10.1126/science.1159806

PubMed ID

  • 18635804

Additional Document Info

start page

  • 408

end page

  • 11


  • 321


  • 5887