Plasmacytoid Dendritic Cells Transport Peripheral Antigens to the Thymus to Promote Central Tolerance

被引：213

作者：

Hadeiba, Husein ^{[1
,2
]}

Lahl, Katharina ^{[1
,2
]}

Edalati, Abdolhossein ^{[1
,2
]}

Oderup, Cecilia ^{[1
,2
]}

Habtezion, Aida ^{[1
,2
]}

Pachynski, Russell ^{[1
,2
]}

Nguyen, Linh ^{[1
,2
]}

Ghodsi, Asma ^{[1
,2
]}

Adler, Sarah ^{[1
,2
]}

Butcher, Eugene C. ^{[1
,2
]}

机构：

[1] Stanford Univ, Sch Med, Dept Pathol, Lab Immunol & Vasc Biol, Stanford, CA 94305 USA

[2] Vet Affairs Palo Alto Hlth Care Syst, Ctr Mol Biol & Med, Palo Alto, CA 94304 USA

来源：

IMMUNITY | 2012年 / 36卷 / 03期

关键词：

T-CELLS; EPITHELIAL-CELLS; HEMATOPOIETIC PROGENITORS; SMALL-INTESTINE; ADULT THYMUS; LYMPH-NODE; EXPRESSION; SELECTION; CCR9; MIGRATION;

D O I：

10.1016/j.immuni.2012.01.017

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Central tolerance can be mediated by peripheral dendritic cells (DCs) that transport innocuous antigens (Ags) to the thymus for presentation to developing T cells, but the responsible DC subsets remained poorly defined. Immature plasmacytoid DCs (pDCs) express CCR9, a chemokine receptor involved in migration of T cell precursors to the thymus. We show here that CCR9 mediated efficient thymic entry of endogenous or i.v. transfused pDCs. pDCs activated by Toll-like receptor (TLR) ligands downregulated CCR9 and lost their ability to home to the thymus. Moreover, endogenous pDCs took up subcutaneously injected fluorescent Ag and, in the absence of TLR signals, transported Ag to the thymus in a CCR9-dependent fashion. Injected, Ag-loaded pDCs effectively deleted Ag-specific thymocytes, and this thymic clonal deletion required CCR9-mediated homing and was prevented by infectious signals. Thus, peripheral pDCs can contribute to immune tolerance through CCR9-dependent transport of peripheral Ags and subsequent deletion of Ag-reactive thymocytes.

引用

页码：438 / 450

页数：13

共 35 条

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