Publication Date:
2008-07-19
Description:
When intracellular pathogens invade mammalian hosts, naive 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807624/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Intlekofer, Andrew M -- Banerjee, Arnob -- Takemoto, Naofumi -- Gordon, Scott M -- Dejong, Caitlin S -- Shin, Haina -- Hunter, Christopher A -- Wherry, E John -- Lindsten, Tullia -- Reiner, Steven L -- AI007532/AI/NIAID NIH HHS/ -- AI042334/AI/NIAID NIH HHS/ -- AI042370/AI/NIAID NIH HHS/ -- AI061699/AI/NIAID NIH HHS/ -- AI071309/AI/NIAID NIH HHS/ -- AI076458/AI/NIAID NIH HHS/ -- R01 AI042370/AI/NIAID NIH HHS/ -- R01 AI042370-12/AI/NIAID NIH HHS/ -- R01 AI061699/AI/NIAID NIH HHS/ -- R01 AI061699-05/AI/NIAID NIH HHS/ -- R01 AI071309/AI/NIAID NIH HHS/ -- R01 AI071309-01/AI/NIAID NIH HHS/ -- R01 AI076458/AI/NIAID NIH HHS/ -- R01 AI076458-02/AI/NIAID NIH HHS/ -- T32 CA009140/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Jul 18;321(5887):408-11. doi: 10.1126/science.1159806.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18635804" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, Viral/immunology
;
Arenaviridae Infections/*immunology/pathology/virology
;
CD4-Positive T-Lymphocytes/immunology
;
CD8-Positive T-Lymphocytes/*immunology/*metabolism
;
Cell Differentiation
;
Cytotoxicity, Immunologic
;
Interferon-gamma/metabolism
;
Interleukin-17/*metabolism
;
Lymphocyte Depletion
;
*Lymphocytic choriomeningitis virus/immunology/isolation &
;
purification/physiology
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
T-Box Domain Proteins/deficiency/genetics/*physiology
;
Virus Replication
;
Wasting Syndrome/immunology/pathology/virology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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