Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity.
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.
Hildner
Kai
K
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Edelson
Brian T
BT
Purtha
Whitney E
WE
Diamond
Mark
M
Matsushita
Hirokazu
H
Kohyama
Masako
M
Calderon
Boris
B
Schraml
Barbara U
BU
Unanue
Emil R
ER
Diamond
Michael S
MS
Schreiber
Robert D
RD
Murphy
Theresa L
TL
Murphy
Kenneth M
KM
D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis*; D045142:Cross-Priming; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology; D014902:West Nile virus / Q000276:immunology
D000914:Antibodies, Viral; D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D012097:Repressor Proteins; C533289:SNFT protein, mouse