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

M. Grusdat, D. R. McIlwain, H. C. Xu, V. I. Pozdeev, J. Knievel, S. Q. Crome, C. Robert-Tissot, R. J. Dress, A. A. Pandyra, D. E. Speiser, E. Lang, S. K. Maney, A. R. Elford, S. R. Hamilton, S. Scheu, K. Pfeffer, J. Bode, H. W. Mittrücker, M. Lohoff, M. HuberD. Häussinger, P. S. Ohashi, T. W. Mak, K. S. Lang, P. A. Lang*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)

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 0. 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.

Original languageEnglish
Pages (from-to)1050-1060
Number of pages11
JournalCell Death and Differentiation
Volume21
Issue number7
DOIs
Publication statusPublished - Jul 2014
Externally publishedYes

Keywords

  • BATF
  • hepatitis
  • immunopathology
  • IRF4
  • LCMV

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