Batf3 Deficiency Reveals a Critical Role for CD8α+ Dendritic Cells in Cytotoxic T Cell Immunity

被引：1545

作者：

Hildner, Kai ^{[1
,2
]}

Edelson, Brian T. ^{[1
]}

Purtha, Whitney E. ^{[3
,4
]}

Diamond, Mark ^{[1
]}

Matsushita, Hirokazu ^{[1
]}

Kohyama, Masako ^{[1
,2
]}

Calderon, Boris ^{[1
]}

Schraml, Barbara U. ^{[1
]}

Unanue, Emil R. ^{[1
]}

Diamond, Michael S. ^{[1
,3
,4
]}

Schreiber, Robert D. ^{[1
]}

Murphy, Theresa L. ^{[1
]}

Murphy, Kenneth M. ^{[1
,2
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

来源：

SCIENCE | 2008年 / 322卷 / 5904期

关键词：

D O I：

10.1126/science.1164206

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：

Although in vitro observations suggest that cross- presentation of antigens is mediated primarily by CD8 alpha(+) dendritic cells, in vivo analysis has been hampered by the lack of systems that selectively eliminate this cell lineage. We show that deletion of the transcription factor Batf3 ablated development of CD8 alpha(+) dendritic cells, allowing us to examine their role in immunity in vivo. Dendritic cells from Batf3(-/-) mice were defective in cross- presentation, and Batf3(-/-) mice lacked virus- specific CD8(+) T cell responses to West Nile virus. Importantly, rejection of highly immunogenic syngeneic tumors was impaired in Batf3(-/-) mice. These results suggest an important role for CD8 alpha(+) dendritic cells and cross- presentation in responses to viruses and in tumor rejection.

引用

页码：1097 / 1100

页数：4

共 29 条

[21] Toll-like receptor 3 promotes cross-priming to virus-infected cells [J].

Schulz, O ;

Diebold, SS ;

Chen, M ;

Näslund, TI ;

Nolte, MA ;

Alexopoulou, L ;

Azuma, YT ;

Flavell, RA ;

Liljeström, P ;

Sousa, CRE .

NATURE, 2005, 433 (7028) :887-892

[22] IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity [J].

Shankaran, V ;

Ikeda, H ;

Bruce, AT ;

White, JM ;

Swanson, PE ;

Old, LJ ;

Schreiber, RD .

NATURE, 2001, 410 (6832) :1107-1111

[23] Steady-state and inflammatory dendritic-cell development [J].

Shortman, Ken ;

Naik, Shalin H. .

NATURE REVIEWS IMMUNOLOGY, 2007, 7 (01) :19-30

[24] CD4+ T-cell responses are required for clearance of West Nile virus from the central nervous system [J].

Sitati, Elizabeth M. ;

Diamond, Michael S. .

JOURNAL OF VIROLOGY, 2006, 80 (24) :12060-12069

[25] A major lung CD103 (αE)-β7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins [J].

Sung, SSJ ;

Fu, SM ;

Rose, CE ;

Gaskin, F ;

Ju, ST ;

Beaty, SR .

JOURNAL OF IMMUNOLOGY, 2006, 176 (04) :2161-2172

[26] Skin-derived dendritic cells can mediate deletional tolerance of class I-Restricted self-reactive T cells [J].

Waithman, Jason ;

Allan, Rhys S. ;

Kosaka, Hiroshi ;

Azukizawa, Hiroaki ;

Shortman, Ken ;

Lutz, Manfred B. ;

Heath, William R. ;

Carbone, Francis R. ;

Belz, Gabrielle T. .

JOURNAL OF IMMUNOLOGY, 2007, 179 (07) :4535-4541

[27] Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity [J].

Wilson, NS ;

Behrens, GMN ;

Lundie, RJ ;

Smith, CM ;

Waithman, J ;

Young, L ;

Forehan, SP ;

Mount, A ;

Steptoe, RJ ;

Shortman, KD ;

de Koning-Ward, TF ;

Belz, GT ;

Carbone, FR ;

Crabb, BS ;

Heath, WR ;

Villadangos, JA .

NATURE IMMUNOLOGY, 2006, 7 (02) :165-172

[28] Redundancy of direct priming and cross-priming in tumor-specific CD8+ T cell responses [J].

Wolkers, MC ;

Stoetter, G ;

Vyth-Dreese, FA ;

Schumacher, TNM .

JOURNAL OF IMMUNOLOGY, 2001, 167 (07) :3577-3584

[29] Towards an understanding of the transcription factor network of dendritic cell development [J].

Zenke, M ;

Hieronymus, T .

TRENDS IN IMMUNOLOGY, 2006, 27 (03) :140-145

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