Origin and differentiation of human memory CD8 T cells after vaccination

被引：400

作者：

Akondy, Rama S. ^{[1
,2
]}

Fitch, Mark ^{[3
]}

Edupuganti, Srilatha ^{[4
]}

Yang, Shu ^{[1
,2
,14
]}

Kissick, Haydn T. ^{[5
]}

Li, Kelvin W. ^{[6
]}

Youngblood, Ben A. ^{[1
,2
,7
]}

Abdelsamed, Hossam A. ^{[7
]}

McGuire, Donald J. ^{[1
]}

Cohen, Kristen W. ^{[8
]}

Alexe, Gabriela ^{[9
,10
]}

Nagar, Shashi ^{[4
]}

McCausland, Megan M. ^{[1
,2
]}

Gupta, Satish ^{[11
]}

Tata, Pramila ^{[11
,15
]}

Haining, W. Nicholas ^{[9
,10
]}

McElrath, M. Juliana ^{[8
]}

Zhang, David ^{[12
]}

Hu, Bin ^{[12
]}

Greenleaf, William J. ^{[13
]}

Goronzy, Jorg J. ^{[12
]}

Mulligan, Mark J. ^{[1
,4
]}

Hellerstein, Marc ^{[3
,6
]}

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] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA

[4] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA

[5] Emory Univ, Sch Med, Dept Urol, Atlanta, GA USA

[6] KineMed Inc, Emeryville, CA 94608 USA

[7] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA

[8] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA

[9] Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[10] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[11] Strand Lifesci, Bangalore, Karnataka, India

[12] Stanford Univ, Dept Med, Div Rheumatol & Immunol, Sch Med, Stanford, CA 94305 USA

[13] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[14] Cent S Univ, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China

[15] Syngene Int, Bangalore, Karnataka, India

来源：

NATURE | 2017年 / 552卷 / 7685期

关键词：

VIRAL-INFECTION; LIFE-SPAN; EFFECTOR; TURNOVER; LYMPHOCYTES; EXHAUSTION;

D O I：

10.1038/nature24633

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The differentiation of human memory CD8 T cells is not well understood. Here we address this issue using the live yellow fever virus (YFV) vaccine, which induces long-term immunity in humans. We used in vivo deuterium labelling to mark CD8 T cells that proliferated in response to the virus and then assessed cellular turnover and longevity by quantifying deuterium dilution kinetics in YFV-specific CD8 T cells using mass spectrometry. This longitudinal analysis showed that the memory pool originates from CD8 T cells that divided extensively during the first two weeks after infection and is maintained by quiescent cells that divide less than once every year (doubling time of over 450 days). Although these long-lived YFV-specific memory CD8 T cells did not express effector molecules, their epigenetic landscape resembled that of effector CD8 T cells. This open chromatin profile at effector genes was maintained in memory CD8 T cells isolated even a decade after vaccination, indicating that these cells retain an epigenetic fingerprint of their effector history and remain poised to respond rapidly upon re-exposure to the pathogen.

引用

页码：362 / +

页数：18

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