A20 Curtails Primary but Augments Secondary CD8(+) T Cell Responses in Intracellular Bacterial Infection.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620930
Title:
A20 Curtails Primary but Augments Secondary CD8(+) T Cell Responses in Intracellular Bacterial Infection.
Authors:
Just, Sissy; Nishanth, Gopala; Buchbinder, Jörn H; Wang, Xu; Naumann, Michael; Lavrik, Inna; Schlüter, Dirk
Abstract:
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7., 38124 Braunschweig, Germany.
Citation:
A20 Curtails Primary but Augments Secondary CD8(+) T Cell Responses in Intracellular Bacterial Infection. 2016, 6:39796 Sci Rep
Journal:
Scientific reports
Issue Date:
22-Dec-2016
URI:
http://hdl.handle.net/10033/620930
DOI:
10.1038/srep39796
PubMed ID:
28004776
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
publications of the scientific administration (GFW)

Full metadata record

DC FieldValue Language
dc.contributor.authorJust, Sissyen
dc.contributor.authorNishanth, Gopalaen
dc.contributor.authorBuchbinder, Jörn Hen
dc.contributor.authorWang, Xuen
dc.contributor.authorNaumann, Michaelen
dc.contributor.authorLavrik, Innaen
dc.contributor.authorSchlüter, Dirken
dc.date.accessioned2017-05-31T14:08:08Z-
dc.date.available2017-05-31T14:08:08Z-
dc.date.issued2016-12-22-
dc.identifier.citationA20 Curtails Primary but Augments Secondary CD8(+) T Cell Responses in Intracellular Bacterial Infection. 2016, 6:39796 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid28004776-
dc.identifier.doi10.1038/srep39796-
dc.identifier.urihttp://hdl.handle.net/10033/620930-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleA20 Curtails Primary but Augments Secondary CD8(+) T Cell Responses in Intracellular Bacterial Infection.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7., 38124 Braunschweig, Germany.en
dc.identifier.journalScientific reportsen

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