Autophagy is essential for effector CD8+ T cell survival and memory formation

被引:350
作者
Xu, Xiaojin [1 ,2 ]
Araki, Koichi [1 ,2 ]
Li, Shuzhao [3 ]
Han, Jin-Hwan [1 ,2 ]
Ye, Lilin [1 ,2 ]
Tan, Wendy G. [1 ,2 ]
Konieczny, Bogumila T. [1 ,2 ]
Bruinsma, Monique W. [4 ]
Martinez, Jennifer [5 ]
Pearce, Erika L. [4 ]
Green, Douglas R. [5 ]
Jones, Dean P. [3 ]
Virgin, Herbert W. [4 ]
Ahmed, Rafi [1 ,2 ]
机构
[1] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
[3] Emory Univ, Sch Med, Dept Med, Div Pulm Allergy & Crit Care, Atlanta, GA USA
[4] Washington Univ, Sch Med, Dept Microbiol & Immunol, St Louis, MO USA
[5] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA
基金
美国国家卫生研究院;
关键词
SELECTIVE AUTOPHAGY; EXPRESSION; PROTEIN; PERSISTENCE; ACTIVATION; MAINTAINS; IL-7;
D O I
10.1038/ni.3025
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The importance of autophagy in the generation of memory CD8(+) T cells in vivo is not well defined. We report here that autophagy was dynamically regulated in virus-specific CD8(+) T cells during acute infection of mice with lymphocytic choriomeningitis virus. In contrast to the current paradigm, autophagy decreased in activated proliferating effector CD8(+) T cells and was then upregulated when the cells stopped dividing just before the contraction phase. Consistent with those findings, deletion of the gene encoding either of the autophagy-related molecules Atg5 or Atg7 had little to no effect on the proliferation and function of effector cells, but these autophagy-deficient effector cells had survival defects that resulted in compromised formation of memory T cells. Our studies define when autophagy is needed during effector and memory differentiation and warrant reexamination of the relationship between T cell activation and autophagy.
引用
收藏
页码:1152 / 1161
页数:10
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