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

Andrew M. Intlekofer, Arnob Banerjee, Naofumi Takemoto, Scott M. Gordon, Caitlin S. DeJong, Haina Shin, Christopher A. Hunter, E. John Wherry, Tullia Lindsten, Steven L. Reiner

Research output: Contribution to journalArticlepeer-review

294 Scopus citations

Abstract

When intracellular pathogens invade mammalian hosts, naïve 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.

Original languageEnglish
Pages (from-to)408-411
Number of pages4
JournalScience
Volume321
Issue number5887
DOIs
StatePublished - Jul 18 2008

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