| First Author | Just S | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 39796 | PubMed ID | 28004776 |
| Mgi Jnum | J:250158 | Mgi Id | MGI:6102571 |
| Doi | 10.1038/srep39796 | Citation | Just S, et al. (2016) A20 Curtails Primary but Augments Secondary CD8(+) T Cell Responses in Intracellular Bacterial Infection. Sci Rep 6:39796 |
| abstractText | The ubiquitin-modifying enzyme A20, an important negative feedback regulator of NF-kappaB, 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. |
