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

Author:

Hildner Kai123,Edelson Brian T.123,Purtha Whitney E.123,Diamond Mark123,Matsushita Hirokazu123,Kohyama Masako123,Calderon Boris123,Schraml Barbara U.123,Unanue Emil R.123,Diamond Michael S.123,Schreiber Robert D.123,Murphy Theresa L.123,Murphy Kenneth M.123

Affiliation:

1. Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

2. Howard Hughes Medical Institute, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

3. Departments of Medicine and Molecular Microbiology, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

Abstract

Although in vitro observations suggest that cross-presentation of antigens is mediated primarily by CD8α + 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 CD8α + 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 CD8α + dendritic cells and cross-presentation in responses to viruses and in tumor rejection.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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