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


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.

SUBMITTER: Intlekofer AM 

PROVIDER: S-EPMC2807624 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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

Intlekofer Andrew M AM   Banerjee Arnob A   Takemoto Naofumi N   Gordon Scott M SM   Dejong Caitlin S CS   Shin Haina H   Hunter Christopher A CA   Wherry E John EJ   Lindsten Tullia T   Reiner Steven L SL  

Science (New York, N.Y.) 20080701 5887


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 a  ...[more]

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