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

Science. 2008 Nov 14;322(5904):1097-100. doi: 10.1126/science.1164206.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Viral / blood
  • Basic-Leucine Zipper Transcription Factors / deficiency
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / physiology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8 Antigens / analysis*
  • Cross-Priming*
  • Cytotoxicity, Immunologic*
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Female
  • Fibrosarcoma / immunology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Spleen / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • West Nile Fever / immunology
  • West Nile virus / immunology

Substances

  • Antibodies, Viral
  • Basic-Leucine Zipper Transcription Factors
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Repressor Proteins
  • SNFT protein, mouse