Progenitor and Terminal Subsets of CD8+ T Cells Cooperate to Contain Chronic Viral Infection

被引：750

作者：

Paley, Michael A. ^{[1
,2
]}

Kroy, Daniela C. ^{[3
]}

Odorizzi, Pamela M. ^{[1
,2
]}

Johnnidis, Jonathan B. ^{[1
,2
]}

Dolfi, Douglas V. ^{[1
,2
]}

Barnett, Burton E. ^{[1
,2
]}

Bikoff, Elizabeth K. ^{[4
]}

Robertson, Elizabeth J. ^{[4
]}

Lauer, Georg M. ^{[3
]}

Reiner, Steven L. ^{[5
,6
]}

Wherry, E. John ^{[1
,2
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA

[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA

[4] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[5] Univ Penn, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA

[6] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA

来源：

SCIENCE | 2012年 / 338卷 / 6111期

关键词：

TRANSCRIPTION FACTOR; PD-1; EXPRESSION; HIV-1; INFECTION; CUTTING EDGE; EXHAUSTION; BET; RESPONSES; ANTIGEN; CD4(+); DIFFERENTIATION;

D O I：

10.1126/science.1229620

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：

07 ; 0710 ; 09 ;

摘要：

Chronic infections strain the regenerative capacity of antiviral T lymphocyte populations, leading to failure in long-term immunity. The cellular and molecular events controlling this regenerative capacity, however, are unknown. We found that two distinct states of virus-specific CD8(+) T cells exist in chronically infected mice and humans. Differential expression of the T-box transcription factors T-bet and Eomesodermin (Eomes) facilitated the cooperative maintenance of the pool of antiviral CD8(+) T cells during chronic viral infection. T-bet(hi) cells displayed low intrinsic turnover but proliferated in response to persisting antigen, giving rise to Eomes(hi) terminal progeny. Genetic elimination of either subset resulted in failure to control chronic infection, which suggests that an imbalance in differentiation and renewal could underlie the collapse of immunity in humans with chronic infections.

引用

页码：1220 / 1225

页数：6

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