T cell exhaustion

被引:3024
作者
Wherry, E. John [1 ]
机构
[1] Univ Penn, Sch Med, Dept Microbiol, Inst Immunol, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
CHRONIC VIRAL-INFECTION; VIRUS-SPECIFIC CD4(+); GROWTH-FACTOR-BETA; HEPATITIS-C; PD-1; EXPRESSION; UP-REGULATION; PROGRAMMED DEATH-1; IMMUNE-RESPONSES; DENDRITIC CELLS; CD8;
D O I
10.1038/ni.2035
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T cell exhaustion is a state of T cell dysfunction that arises during many chronic infections and cancer. It is defined by poor effector function, sustained expression of inhibitory receptors and a transcriptional state distinct from that of functional effector or memory T cells. Exhaustion prevents optimal control of infection and tumors. Recently, a clearer picture of the functional and phenotypic profile of exhausted T cells has emerged and T cell exhaustion has been defined in many experimental and clinical settings. Although the pathways involved remain to be fully defined, advances in the molecular delineation of T cell exhaustion are clarifying the underlying causes of this state of differentiation and also suggest promising therapeutic opportunities.
引用
收藏
页码:492 / 499
页数:8
相关论文
共 117 条
[1]   Impaired NFAT nuclear translocation results in split exhaustion of virus-specific CD8+ T cell functions during chronic viral infection [J].
Agnellini, Paola ;
Wolint, Petra ;
Rehr, Manuela ;
Cahenzli, Julia ;
Karrer, Urs ;
Oxenius, Annette .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (11) :4565-4570
[2]   Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? [J].
Akbar, Arne N. ;
Henson, Sian M. .
NATURE REVIEWS IMMUNOLOGY, 2011, 11 (04) :289-295
[3]   Hepatitis C virus (HCV)-specific CD8+ cells produce transforming growth factor β that can suppress HCV-specific T-cell responses [J].
Alatrakchi, Nadia ;
Graham, Camilla S. ;
van der Vliet, Hans J. J. ;
Sherman, Kenneth E. ;
Exley, Mark A. ;
Koziel, Margaret James .
JOURNAL OF VIROLOGY, 2007, 81 (11) :5882-5892
[4]   TH cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes [J].
Avni, O ;
Lee, D ;
Macian, F ;
Szabo, SJ ;
Glimcher, LH ;
Rao, A .
NATURE IMMUNOLOGY, 2002, 3 (07) :643-651
[5]   Restoring function in exhausted CD8 T cells during chronic viral infection [J].
Barber, DL ;
Wherry, EJ ;
Masopust, D ;
Zhu, BG ;
Allison, JP ;
Sharpe, AH ;
Freeman, GJ ;
Ahmed, R .
NATURE, 2006, 439 (7077) :682-687
[6]   Natural regulatory T cells in infectious disease [J].
Belkaid, Y ;
Rouse, BT .
NATURE IMMUNOLOGY, 2005, 6 (04) :353-360
[7]   HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells [J].
Betts, Michael R. ;
Nason, Martha C. ;
West, Sadie M. ;
De Rosa, Stephen C. ;
Migueles, Stephen A. ;
Abraham, Jonathan ;
Lederman, Michael M. ;
Benito, Jose M. ;
Goepfert, Paul A. ;
Connors, Mark ;
Roederer, Mario ;
Koup, Richard A. .
BLOOD, 2006, 107 (12) :4781-4789
[8]   An expanding job description for Blimp-1/PRDM1 [J].
Bikoff, Elizabeth K. ;
Morgan, Marc A. ;
Robertson, Elizabeth J. .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2009, 19 (04) :379-385
[9]   IL-10, T cell exhaustion and viral persistence [J].
Blackburn, Shawn D. ;
Wherry, E. John .
TRENDS IN MICROBIOLOGY, 2007, 15 (04) :143-146
[10]   Tissue-Specific Differences in PD-1 and PD-L1 Expression during Chronic Viral Infection: Implications for CD8 T-Cell Exhaustion [J].
Blackburn, Shawn D. ;
Crawford, Alison ;
Shin, Haina ;
Polley, Antonio ;
Freeman, Gordon J. ;
Wherry, E. John .
JOURNAL OF VIROLOGY, 2010, 84 (04) :2078-2089