Regulatory T Cells Sequentially Migrate from Inflamed Tissues to Draining Lymph Nodes to Suppress the Alloimmune Response

被引：345

作者：

Zhang, Nan ^{[1
,2
]}

Schroeppel, Bernd ^{[2
,3
]}

Lal, Girdhari ^{[1
]}

Jakubzick, Claudia ^{[1
]}

Mao, Xia ^{[1
]}

Chen, Dan ^{[1
]}

Yin, Na ^{[1
]}

Jessberger, Rolf ^{[1
,5
]}

Ochando, Jordi C. ^{[1
,2
,6
]}

Ding, Yaozhong ^{[1
,2
,4
]}

Bromberg, Jonathan S. ^{[1
,2
,4
]}

机构：

[1] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Recanati Miller Transplantat Inst, New York, NY 10029 USA

[3] Mt Sinai Sch Med, Div Nephrol, New York, NY 10029 USA

[4] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA

[5] Tech Univ Dresden, Dept Physiol Chem, D-01307 Dresden, Germany

[6] Inst Salud Carlos III, Unidad Immunol Trasplantes, Ctr Nacl Microbiol, Madrid 28220, Spain

来源：

IMMUNITY | 2009年 / 30卷 / 03期

关键词：

DENDRITIC CELLS; L-SELECTIN; CHEMOKINE RECEPTOR; IMMUNE-RESPONSE; NAIVE-LIKE; FUC-TVII; IN-VIVO; CCR7; INHIBIT; MICE;

D O I：

10.1016/j.immuni.2008.12.022

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

To determine the site and mechanism of suppression by regulatory T (Treg) cells, we investigated their migration and function in an islet allograft model. Treg cells first migrated from blood to the inflamed allograft where they were essential for the suppression of alloimmunity. This process was dependent on the chemokine receptors CCR2, CCR4, and CCR5 and P- and E-selectin ligands. In the allograft, Treg cells were activated and subsequently migrated to the draining lymph nodes (dLNs) in a CCR2, CCR5, and CCR7 fashion; this movement was essential for optimal suppression. Treg cells inhibited dendritic cell migration in a TGF-beta and IL-10 dependent fashion and suppressed antigen-specific T effector cell migration, accumulation, and proliferation in dLNs and allografts. These results showed that sequential migration from blood to the target tissue and to dLNs is required for Treg cells to differentiate and execute fully their suppressive function.

引用

页码：458 / 469

页数：12

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