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  4. Altered T-bet dominance in IFN-γ-decoupled CD4+ T cells with attenuated cytokine storm and preserved memory in influenza
 
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Altered T-bet dominance in IFN-γ-decoupled CD4+ T cells with attenuated cytokine storm and preserved memory in influenza

Journal
Journal of immunology (Baltimore, Md. : 1950)
Journal Volume
190
Journal Issue
8
Pages
4205
Date Issued
2013-04-15
Author(s)
Dutta, Avijit
SHI-CHUEN MIAW  
Yu, Jhang-Sian
Chen, Tse-Ching
Lin, Chun-Yen
Lin, Yung-Chang
Chang, Chia-Shiang
He, Yueh-Chia
Chuang, Sheng-Hao
Yen, Ming-I
Huang, Ching-Tai
DOI
10.4049/jimmunol.1202434
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84875983691&doi=10.4049%2fjimmunol.1202434&partnerID=40&md5=000e1975199fdf4bbe12f9a89a5c03d1
https://scholars.lib.ntu.edu.tw/handle/123456789/416274
URL
https://api.elsevier.com/content/abstract/scopus_id/84875983691
Abstract
Cytokine storm has been postulated as one of the major causes of mortality in patients with severe respiratory viral infections such as influenza. With the help of an influenza Ag- specific mouse experimental system, we report that CD4(+) T cells contribute effector cytokines leading to lung inflammation in acute influenza. Although virus can no longer be detected from tissues 14 d postinfection, virus-derived Ag continues to drive a CD4(+) T cell response after viral clearance. Ag-specific CD4(+) T cells proliferate and evolve into memory CD4(+) T cells efficiently, but the production of effector cytokines is seriously hampered during this phase. This decoupling of proliferation and effector cytokine production doesn't appear in conjunction with increased suppression by regulatory T cells or decreased induction of transcription factors. Rather, GATA-3 and ROR-γt levels are elevated when compared with cells that have effector cytokine production. T-bet dominance over GATA-3 and ROR-γt decreases with the disarmament of effector cytokine production. Importantly, upon reinfection, these decoupled cells produce elevated levels of IFN-γ and were effective in virus eradication. These results provide a mechanism through altered T-bet dominance to dampen the cytokine storm without impeding the generation of memory T cells in influenza virus infection.
Type
journal article

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