A20 Curtails Primary but Augments Secondary CD8 T Cell Responses in Intracellular Bacterial Infection

Overview

Journal Sci Rep

Specialty Science

Date 2016 Dec 23

PMID 28004776

Citations 11

Authors

Sissy Just

Gopala Nishanth

Jorn H Buchbinder

Xu Wang

Michael Naumann

Inna Lavrik

Dirk Schluter

Affiliations

Soon will be listed here.

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) 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 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.

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