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

被引:351
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
相关论文
共 44 条
[31]   Autophagy modulation as a potential therapeutic target for diverse diseases [J].
Rubinsztein, David C. ;
Codogno, Patrice ;
Levine, Beth .
NATURE REVIEWS DRUG DISCOVERY, 2012, 11 (09) :709-U84
[32]   Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates [J].
Sarkar, Surojit ;
Kalia, Vandana ;
Haining, W. Nicholas ;
Konieczny, Bogumila T. ;
Subramaniam, Shruti ;
Ahmed, Rafi .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (03) :625-640
[33]   Utilizing flow cytometry to monitor autophagy in living mammalian cells [J].
Shvets, Elena ;
Fass, Ephraim ;
Elazar, Zvulun .
AUTOPHAGY, 2008, 4 (05) :621-628
[34]   Autophagy regulates lipid metabolism [J].
Singh, Rajat ;
Kaushik, Susmita ;
Wang, Yongjun ;
Xiang, Youqing ;
Novak, Inna ;
Komatsu, Masaaki ;
Tanaka, Keiji ;
Cuervo, Ana Maria ;
Czaja, Mark J. .
NATURE, 2009, 458 (7242) :1131-U64
[35]   Identification of Atg5-dependent transcriptional changes and increases in mitochondrial mass in Atg5-deficient T lymphocytes [J].
Stephenson, Linda M. ;
Miller, Brian C. ;
Ng, Aylwin ;
Eisenberg, Jason ;
Zhao, Zijiang ;
Cadwell, Ken ;
Graham, Daniel B. ;
Mizushima, Noboru N. ;
Xavier, Ramnik ;
Virgin, Herbert W. ;
Swat, Wojciech .
AUTOPHAGY, 2009, 5 (05) :625-635
[36]   Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles [J].
Subramanian, A ;
Tamayo, P ;
Mootha, VK ;
Mukherjee, S ;
Ebert, BL ;
Gillette, MA ;
Paulovich, A ;
Pomeroy, SL ;
Golub, TR ;
Lander, ES ;
Mesirov, JP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) :15545-15550
[37]   Mitochondrial Respiratory Capacity Is a Critical Regulator of CD8+ T Cell Memory Development [J].
van der Windt, Gerritje J. W. ;
Everts, Bart ;
Chang, Chih-Hao ;
Curtis, Jonathan D. ;
Freitas, Tori C. ;
Amiel, Eyal ;
Pearce, Edward J. ;
Pearce, Erika L. .
IMMUNITY, 2012, 36 (01) :68-78
[38]   Natural killer cells act as rheostats modulating antiviral T cells [J].
Waggoner, Stephen N. ;
Cornberg, Markus ;
Selin, Liisa K. ;
Welsh, Raymond M. .
NATURE, 2012, 481 (7381) :394-U183
[39]   The complex interplay between autophagy, apoptosis, and necrotic signals promotes T-cell homeostasis [J].
Walsh, Craig M. ;
Edinger, Aimee L. .
IMMUNOLOGICAL REVIEWS, 2010, 236 :95-109
[40]   Autophagy in cellular growth control [J].
Wang, Richard C. ;
Levine, Beth .
FEBS LETTERS, 2010, 584 (07) :1417-1426