Cutting Edge: The Transcription Factor Eomesodermin Enables CD8+ T Cells To Compete for the Memory Cell Niche

被引:319
作者
Banerjee, Arnob [1 ,2 ]
Gordon, Scott M. [1 ,2 ]
Intlekofer, Andrew M. [1 ,2 ]
Paley, Michael A. [3 ]
Mooney, Erin C. [1 ,2 ]
Lindsten, Tulia [1 ,4 ]
Wherry, E. John [3 ]
Reiner, Steven L. [1 ,2 ]
机构
[1] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Med, Philadelphia, PA 19104 USA
[3] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
[4] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
BONE-MARROW; BET; EFFECTOR; DIFFERENTIATION; EXPRESSION; SUBSETS; SITE;
D O I
10.4049/jimmunol.1002042
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD8(+) T cells responding to intracellular infection give rise to cellular progeny that become terminally differentiated effector cells and self-renewing memory cells. T-bet and eomesodermin (Eomes) are key transcription factors of cytotoxic lymphocyte lineages. We show in this study that CD8(+) T cells lacking Eomes compete poorly in contributing to the pool of Ag-specific central memory cells. Eomes-deficient CD8(+) T cells undergo primary clonal expansion but are defective in long-term survival, populating the bone marrow niche and re-expanding postrechallenge. The phenotype of Eomes-deficient CD8(+) T cells supports the hypothesis that T-bet and Eomes can act redundantly to induce effector functions, but can also act to reciprocally promote terminal differentiation versus self-renewal of Ag-specific memory cells. The Journal of Immunology, 2010, 185: 4988-4992.
引用
收藏
页码:4988 / 4992
页数:5
相关论文
共 14 条
[1]   Bone marrow is a preferred site for homeostatic proliferation of memory CD8 T cells [J].
Becker, TC ;
Coley, SM ;
Wherry, EJ ;
Ahmed, R .
JOURNAL OF IMMUNOLOGY, 2005, 174 (03) :1269-1273
[2]   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
[3]   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
[4]   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
[5]   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
[6]   CMV-specific central memory T cells reside in bone marrow [J].
Letsch, Anne ;
Knoedler, Maren ;
Na, Il-Kang ;
Kern, Florian ;
Asemissen, Anne-Marie ;
Keilholz, Ulrich ;
Loesch, Michael ;
Thiel, Eckhard ;
Volk, Hans-Dieter ;
Scheibenbogen, Carmen .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2007, 37 (11) :3063-3068
[7]   Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells [J].
Mazo, IB ;
Honczarenko, M ;
Leung, H ;
Cavanagh, LL ;
Bonasio, R ;
Weninger, W ;
Engelke, K ;
Xia, LJ ;
McEver, RP ;
Koni, PA ;
Silberstein, LE ;
von Andrian, UH .
IMMUNITY, 2005, 22 (02) :259-270
[8]   CD8 cell division maintaining cytotoxic memory occurs predominantly in the bone marrow [J].
Parretta, E ;
Cassese, G ;
Barba, P ;
Santoni, A ;
Guardiola, J ;
Di Rosa, F .
JOURNAL OF IMMUNOLOGY, 2005, 174 (12) :7654-7664
[9]   Control of effector CD8+ T cell function by the transcription factor Eomesodermin [J].
Pearce, EL ;
Mullen, AC ;
Martins, GA ;
Krawczyk, CM ;
Hutchins, AS ;
Zediak, VP ;
Banica, M ;
DiCioccio, CB ;
Gross, DA ;
Mao, C ;
Shen, H ;
Cereb, N ;
Yang, SY ;
Lindsten, T ;
Rossant, J ;
Hunter, CA ;
Reiner, SL .
SCIENCE, 2003, 302 (5647) :1041-1043
[10]   The mTOR Kinase Determines Effector versus Memory CD8+ T Cell Fate by Regulating the Expression of Transcription Factors T-bet and Eomesodermin [J].
Rao, Rajesh R. ;
Li, Qingsheng ;
Odunsi, Kunle ;
Shrikant, Protul A. .
IMMUNITY, 2010, 32 (01) :67-78