Format

Send to

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

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

Author information

1
Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
2
1] Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany [2] Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
3
Department of Medical Biophysics and Immunology, Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), University of Toronto, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1.
4
Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
5
Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
6
1] Department of Medical Biophysics and Immunology, Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), University of Toronto, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1 [2] Clinical Tumor Biology & Immunotherapy Group, Department of Oncology and Ludwig Center for Cancer Research, University of Lausanne HO-05/1552, Av. P.-Decker 4, CH-1011 Lausanne, Switzerland.
7
Institute for Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
8
Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, Germany.

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.

PMID:
24531538
PMCID:
PMC4207473
DOI:
10.1038/cdd.2014.19
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center