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PMID: 19008445 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity.

Science (New York, N.Y.) ·Vol. 322 ·No. 5904 ·2008-11-14 ·Pages 1097-100

Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, Schreiber RD, Murphy TL, Murphy KM

Abstract

Although in vitro observations suggest that cross-presentation of antigens is mediated primarily by CD8alpha+ 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 CD8alpha+ 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 CD8alpha+ dendritic cells and cross-presentation in responses to viruses and in tumor rejection.

MeSH Terms
Adoptive Transfer Animals Antibodies, Viral/blood Basic-Leucine Zipper Transcription Factors/deficiency,genetics,physiology CD4-Positive T-Lymphocytes/immunology CD8 Antigens/analysis Cross-Priming Cytotoxicity, Immunologic Dendritic Cells/immunology,transplantation Female Fibrosarcoma/immunology Lymphocyte Activation Male Mice Mice, Inbred C57BL Repressor Proteins/genetics,physiology Spleen/immunology T-Lymphocytes, Cytotoxic/immunology West Nile Fever/immunology West Nile virus/immunology
Chemicals
Antibodies, Viral Basic-Leucine Zipper Transcription Factors CD8 Antigens CD8 antigen, alpha chain Repressor Proteins SNFT protein, mouse
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Hildner Kai
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Edelson Brian T
Purtha Whitney E
Diamond Mark
Matsushita Hirokazu
Kohyama Masako
Calderon Boris
Schraml Barbara U
Unanue Emil R
Diamond Michael S
Schreiber Robert D
Murphy Theresa L
Murphy Kenneth M
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1164206
Published
2008-11-14
Pages
1097-100
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2756611
Subset
IM
Grants
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1126/science.1164206 PMC Full Text View journal details
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