Decrease of Foxp3+ Treg Cell Number and Acquisition of Effector Cell Phenotype during Lethal Infection

被引：472

作者：

Oldenhove, Guillaume ^{[1
]}

Bouladoux, Nicolas ^{[1
]}

Wohlfert, Elizabeth A. ^{[1
]}

Hall, Jason A. ^{[1
,5
]}

Chou, David ^{[1
]}

Dos Santos, Liliane ^{[1
]}

O'Brien, Shaun ^{[5
]}

Blank, Rebecca ^{[1
]}

Lamb, Erika ^{[3
]}

Natarajan, Sundar ^{[3
]}

Kastenmayer, Robin ^{[2
]}

Hunter, Christopher ^{[4
]}

Grigg, Michael E. ^{[3
]}

Belkaid, Yasmine ^{[1
]}

机构：

[1] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA

[2] NIAID, Comparat Med Branch, Bill Young Ctr Biodefense & Emerging Infect Dis, NIH, Bethesda, MD 20892 USA

[3] NIAID, Mol Parasitol Unit, NIH, Bethesda, MD 20892 USA

[4] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA

[5] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA

来源：

IMMUNITY | 2009年 / 31卷 / 05期

基金：

美国国家卫生研究院;

关键词：

REGULATORY T-CELLS; DENDRITIC CELLS; IFN-GAMMA; TOXOPLASMA-GONDII; PERORAL INFECTION; SMALL-INTESTINE; C57BL/6; MICE; TGF-BETA; RESISTANCE; TOLERANCE;

D O I：

10.1016/j.immuni.2009.10.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Using a model of lethal oral infection with Toxoplasma gondii, we examined the fate of both induced and natural regulatory T (Treg) cells in the face of strong inflammatory responses occurring in a tolerogenicprone environment. We found that during highly T helper 1 (Th1) cell-polarized mucosal immune responses, Treg cell numbers collapsed via multiple pathways, including blockade of Treg cell induction and disruption of endogenous Treg cell homeostasis. In particular, shutdown of interleukin 2 (IL-2) in the highly Th1 cell-polarized environment triggered by infection directly contributes to Treg cell incapacity to suppress effector responses and eventually leads to immunopathogenesis. Furthermore, we found that environmental cues provided by both local dendritic cells and effector T cells can induce the expression of T-bet transcription factor and IFN-gamma by Treg cells. These data reveal a mechanism for Th1 cell pathogenicity that extends beyond their proinflammatory program to limit Treg cell survival.

引用

页码：772 / 786

页数：15

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