Transcriptional Repressor Blimp-1 Promotes CD8+ T Cell Terminal Differentiation and Represses the Acquisition of Central Memory T Cell Properties

被引:476
作者
Rutishauser, Rachel L. [1 ]
Martins, Gislaine A. [3 ]
Kalachikov, Sergey [2 ]
Chandele, Anmol [1 ]
Parish, Ian A. [1 ]
Meffre, Eric [1 ]
Jacob, Joshy [4 ]
Calame, Kathryn [3 ]
Kaech, Susan M. [1 ]
机构
[1] Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA
[2] Columbia Univ, Coll Phys & Surg, Columbia Genome Ctr, New York, NY 10032 USA
[3] Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA
[4] Emory Univ, Sch Med, Dept Microbiol & Immunol, Emory Vaccine Ctr,Yerkes Natl Primate Ctr, Atlanta, GA 30322 USA
关键词
CHRONIC VIRAL-INFECTION; IL-7; RECEPTOR-ALPHA; IN-VIVO; B-CELLS; SELECTIVE EXPRESSION; LINEAGE RELATIONSHIP; GENE-EXPRESSION; EFFECTOR; HOMEOSTASIS; GENERATION;
D O I
10.1016/j.immuni.2009.05.014
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
During acute infections, a small population of effector CD8(+) T cells evades terminal differentiation and survives as long-lived memory T cells. We demonstrate that the transcriptional repressor Blimp-1 enhanced the formation of terminally differentiated CD8(+) T cells during lymphocytic choriomeningitis virus (LCMV) infection, and Blimp-1 deficiency promoted the acquisition of memory cell properties by effector cells. Blimp-1 expression was preferentially increased in terminally differentiated effector and "effector memory" (Tem) CD8(+) T cells, and gradually decayed after infection as central memory (Tcm) cells developed. Blimp-1-deficient effector CD8(+) T cells showed some reduction in effector molecule expression, but primarily developed into memory precursor cells that survived better and more rapidly acquired several Tcm cell attributes, including CD62L and IL-2 expression and enhanced proliferative responses. These results reveal a critical role for Blimp-1 in controlling terminal differentiation and suppressing memory cell developmental potential in effector CD8(+) T cells during viral infection.
引用
收藏
页码:296 / 308
页数:13
相关论文
共 61 条
[21]   Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells [J].
Ichii, H ;
Sakamoto, A ;
Hatano, M ;
Okada, S ;
Toyama, H ;
Taki, S ;
Arima, M ;
Kuroda, Y ;
Tokuhisa, T .
NATURE IMMUNOLOGY, 2002, 3 (06) :558-563
[22]   Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin [J].
Intlekofer, AM ;
Takemoto, N ;
Wherry, EJ ;
Longworth, SA ;
Northrup, JT ;
Palanivel, VR ;
Mullen, AC ;
Gasink, CR ;
Kaech, SM ;
Miller, JD ;
Gapin, L ;
Ryan, K ;
Russ, AP ;
Lindsten, T ;
Orange, JS ;
Goldrath, AW ;
Ahmed, R ;
Reiner, SL .
NATURE IMMUNOLOGY, 2005, 6 (12) :1236-1244
[23]   Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin [J].
Intlekofer, Andrew M. ;
Banerjee, Arnob ;
Takemoto, Naofumi ;
Gordon, Scott M. ;
DeJong, Caitlin S. ;
Shin, Haina ;
Hunter, Christopher A. ;
Wherry, E. John ;
Lindsten, Tullia ;
Reiner, Steven L. .
SCIENCE, 2008, 321 (5887) :408-411
[24]   Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells [J].
Intlekofer, Andrew M. ;
Takemoto, Naofumi ;
Kao, Charlly ;
Banerjee, Arnob ;
Schambach, Felix ;
Northrop, John K. ;
Shen, Hao ;
Wherry, E. John ;
Reiner, Steven L. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (09) :2015-2021
[25]   Modelling T-cell memory by genetic marking of memory T cells in vivo [J].
Jacob, J ;
Baltimore, D .
NATURE, 1999, 399 (6736) :593-597
[26]   Inflammation directs memory precursor and short-lived effector CD8+ T cell fates via the graded expression of T-bet transcription factor [J].
Joshi, Nikhil S. ;
Cui, Weiguo ;
Chandele, Anmol ;
Lee, Heung Kyu ;
Urso, David R. ;
Hagman, James ;
Gapin, Laurent ;
Kaech, Susan M. .
IMMUNITY, 2007, 27 (02) :281-295
[27]   Molecular and functional profiling of memory CD8 T cell differentiation [J].
Kaech, SM ;
Hemby, S ;
Kersh, E ;
Ahmed, R .
CELL, 2002, 111 (06) :837-851
[28]   Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells [J].
Kaech, SM ;
Tan, JT ;
Wherry, EJ ;
Konieczny, BT ;
Surh, CD ;
Ahmed, R .
NATURE IMMUNOLOGY, 2003, 4 (12) :1191-1198
[29]   Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection [J].
Kaech, Susan M. ;
Wherry, E. John .
IMMUNITY, 2007, 27 (03) :393-405
[30]   Transcriptional repressor Blimp-1 is essential for T cell homeostasis and self-tolerance [J].
Kallies, A ;
Hawkins, ED ;
Belz, GT ;
Metcalf, D ;
Hommel, M ;
Corcoran, LM ;
Hodgkin, PD ;
Nutt, SL .
NATURE IMMUNOLOGY, 2006, 7 (05) :466-474