IL-15 activates telomerase and minimizes telomere loss and may preserve the replicative life span of memory CD8+ T cells in vitiro

被引:51
作者
Li, Y [1 ]
Zhi, W [1 ]
Wareski, P [1 ]
Weng, NP [1 ]
机构
[1] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA
关键词
D O I
10.4049/jimmunol.174.7.4019
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 preservation of the replicative life span of memory CD8(+) T cells is vital for long-term immune protection. Although IL-15 plays a key role in the homeostasis of memory CD8(+) T cells, it is unknown whether IL-15 regulates the replicative life span of memory CD8(+) T cells. In this study, we report an analysis of telomerase expression and telomere length in human memory phenotype CD8(+) T cells maintained by IL-15 in vitro. We demonstrate that IL-15 is capable of activating telomerase in memory CD8(+) T cells via Jak3 and PI3K signaling pathways..;urthermore, IL-15 induces a sustained level of telomerase activity over long periods of time, and in turn minimizes telomere loss ii memory CD8(+) T cells after substantial cell divisions. These findings suggest that IL-15 activates stable telomerase expression art I compensates telomere loss in memory phenotype CD8(+) T cells, and that telornerase may play anJimportant role in memory CD8(+) T cell homeostasis.
引用
收藏
页码:4019 / 4024
页数:6
相关论文
共 37 条
[1]   Switching and signaling at the telomere [J].
Blackburn, EH .
CELL, 2001, 106 (06) :661-673
[2]   Mechanism of telomerase induction during T cell activation [J].
Bodnar, AG ;
Kim, NW ;
Effros, RB ;
Chiu, CP .
EXPERIMENTAL CELL RESEARCH, 1996, 228 (01) :58-64
[3]   TELOMERE LENGTH AND REPLICATIVE AGING IN HUMAN VASCULAR TISSUES [J].
CHANG, E ;
HARLEY, CB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (24) :11190-11194
[4]   Interleukin 15: biology and relevance to human disease [J].
Fehniger, TA ;
Caligiuri, MA .
BLOOD, 2001, 97 (01) :14-32
[5]   Telomere length regulation [J].
Greider, CW .
ANNUAL REVIEW OF BIOCHEMISTRY, 1996, 65 :337-365
[6]  
HIYAMA K, 1995, J IMMUNOL, V155, P3711
[7]   Telomeres in T and B cells [J].
Hodes, RJ ;
Hathcock, KS ;
Weng, NP .
NATURE REVIEWS IMMUNOLOGY, 2002, 2 (09) :699-706
[8]   Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase [J].
Hooijberg, E ;
Ruizendaal, JJ ;
Snijders, PJF ;
Kueter, EWM ;
Walboomers, JMM ;
Spits, H .
JOURNAL OF IMMUNOLOGY, 2000, 165 (08) :4239-4245
[9]   Potent induction of long-term CD8+ T cell memory by short-term IL-4 exposure during T cell receptor stimulation [J].
Huang, LR ;
Chen, FL ;
Chen, YT ;
Lin, YM ;
Kung, JT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3406-3411
[10]   Interleukin 15 controls both proliferation and survival of a subset of memory-phenotype CD8+ T cells [J].
Judge, AD ;
Zhang, XH ;
Fujii, H ;
Surh, CD ;
Sprent, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (07) :935-946