Delayed expansion and contraction of CD8+ T cell response during infection with virulent Salmonella typhimurium

被引:47
|
作者
Luu, Rachel A.
Gurnani, Komal
Dudani, Renu
Kammara, Rajagopal
van Faassen, Henk
Sirard, Jean-Claude
Krishnan, Lakshmi
Sad, Subash
机构
[1] Natl Res Council Canada, Inst Biol Sci, Cellular Immunol Lab, Ottawa, ON K1A 0R6, Canada
[2] INSERM, Inst Biol, F-59045 Lille, France
[3] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1N 6N5, Canada
来源
JOURNAL OF IMMUNOLOGY | 2006年 / 177卷 / 03期
基金
加拿大健康研究院;
关键词
D O I
10.4049/jimmunol.177.3.1516
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ag presentation to CD8(+) T cells often commences, immediately after infection, which facilitates their rapid expansion and control of infection. Subsequently, the primed cells undergo rapid contraction. We report that this paradigm is not followed during infection with virulent Salmonella enterica, serovar Typhimurium (ST), an intracellular bacterium that replicates within phagosomes of infected cells. Although susceptible mice die rapidly (similar to 7 days), resistant mice (129x1Svj) harbor a chronic infection lasting similar to 60-90 days. Using rOVA-expressing ST (ST-OVA), we show that T cell priming is considerably delayed in the resistant mice. CD8(+) T cells that are induced during ST-OVA infection undergo delayed expansion, which peaks around day 21, and is followed by protracted contraction. Initially, ST-OVA induces a small population of cycling central phenotype (CD62L(high)IL-7R alpha(high)CD44(high)) CD8(+) T cells. However, by day 14-21, majority of the primed CD8(+) T cells display an effector phenotype (CD62L(low)IL-7R alpha(low)CD44(high)). Subsequently, a progressive increase in the numbers of effector memory phenotype cells (CD62L(low)IL-7R alpha(high)CD44(high)) occurs. This differentiation program remained unchanged after accelerated removal of the pathogen with antibiotics, as majority of the primed cells displayed an effector memory phenotype even at 6 mo postinfection. Despite the chronic infection, CD8(+) T cells induced by ST-OVA were functional as they exhibited killing ability and cytokine production. Importantly, even memory CD8(+) T cells failed to undergo rapid expansion in response to ST-OVA infection, suggesting a delay in T cell priming during infection with virulent ST-OVA. Thus, phagosomal lifestyle may allow escape from host CD8(+) T cell recognition, conferring a survival advantage to the pathogen.
引用
收藏
页码:1516 / 1525
页数:10
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