IRF4 and BATF are critical for CD8⁺ T-cell function following infection with LCMV

Cell Death Differ. 2014 Jul;21(7):1050-60. doi: 10.1038/cdd.2014.19. Epub 2014 Feb 14.

Abstract

CD8(+) T-cell functions are critical for preventing chronic viral infections by eliminating infected cells. For healthy immune responses, beneficial destruction of infected cells must be balanced against immunopathology resulting from collateral damage to tissues. These processes are regulated by factors controlling CD8(+) T-cell function, which are still incompletely understood. Here, we show that the interferon regulatory factor 4 (IRF4) and its cooperating binding partner B-cell-activating transcription factor (BATF) are necessary for sustained CD8(+) T-cell effector function. Although Irf4(-/-) CD8(+) T cells were initially capable of proliferation, IRF4 deficiency resulted in limited CD8(+) T-cell responses after infection with the lymphocytic choriomeningitis virus. Consequently, Irf4(-/-) mice established chronic infections, but were protected from fatal immunopathology. Absence of BATF also resulted in reduced CD8(+) T-cell function, limited immunopathology, and promotion of viral persistence. These data identify the transcription factors IRF4 and BATF as major regulators of antiviral cytotoxic T-cell immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Basic-Leucine Zipper Transcription Factors / physiology*
  • CD8-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Immunologic Memory
  • Interferon Regulatory Factors / physiology*
  • Lymphocyte Activation
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice, Inbred C57BL
  • Mice, Knockout

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • Interferon Regulatory Factors
  • interferon regulatory factor-4