A20 Curtails Primary but Augments Secondary CD8(+) T Cell Responses in Intracellular Bacterial Infection.
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Authors
Just, SissyNishanth, Gopala
Buchbinder, Jörn H
Wang, Xu
Naumann, Michael
Lavrik, Inna
Schlüter, Dirk
Issue Date
2016-12-22
Metadata
Show full item recordAbstract
The ubiquitin-modifying enzyme A20, an important negative feedback regulator of NF-κB, impairs the expansion of tumor-specific CD8(+) T cells but augments the proliferation of autoimmune CD4(+) T cells. To study the T cell-specific function of A20 in bacterial infection, we infected T cell-specific A20 knockout (CD4-Cre A20(fl/fl)) and control mice with Listeria monocytogenes. A20-deficient pathogen-specific CD8(+) T cells expanded stronger resulting in improved pathogen control at day 7 p.i. Imaging flow cytometry revealed that A20-deficient Listeria-specific CD8(+) T cells underwent increased apoptosis and necroptosis resulting in reduced numbers of memory CD8(+) T cells. In contrast, the primary CD4(+) T cell response was A20-independent. Upon secondary infection, the increase and function of pathogen-specific CD8(+) T cells, as well as pathogen control were significantly impaired in CD4-Cre A20(fl/fl) mice. In vitro, apoptosis and necroptosis of Listeria-specific A20-deficient CD8(+) T cells were strongly induced as demonstrated by increased caspase-3/7 activity, RIPK1/RIPK3 complex formation and more morphologically apoptotic and necroptotic CD8(+) T cells. In vitro, A20 limited CD95L and TNF-induced caspase3/7 activation. In conclusion, T cell-specific A20 limited the expansion but reduced apoptosis and necroptosis of Listeria-specific CD8(+) T cells, resulting in an impaired pathogen control in primary but improved clearance in secondary infection.Citation
A20 Curtails Primary but Augments Secondary CD8(+) T Cell Responses in Intracellular Bacterial Infection. 2016, 6:39796 Sci RepAffiliation
Helmholtz Centre for infection research, Inhoffenstr. 7., 38124 Braunschweig, Germany.Journal
Scientific reportsPubMed ID
28004776Type
ArticleLanguage
enISSN
2045-2322ae974a485f413a2113503eed53cd6c53
10.1038/srep39796
Scopus Count
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/