title: IRF4 and BATF are critical for CD8⁺ T-cell function following infection with LCMV.
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.
authors: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: M
authors: M
authors: Grusdat
authors: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: D R
authors: DR
authors: McIlwain
authors: 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.
authors: H C
authors: HC
authors: Xu
authors: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: V I
authors: VI
authors: Pozdeev
authors: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: J
authors: J
authors: Knievel
authors: 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.
authors: S Q
authors: SQ
authors: Crome
authors: 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.
authors: C
authors: C
authors: Robert-Tissot
authors: Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: R J
authors: RJ
authors: Dress
authors: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors: A A
authors: AA
authors: Pandyra
authors: 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.
authors: D E
authors: DE
authors: Speiser
authors: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: E
authors: E
authors: Lang
authors: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: S K
authors: SK
authors: Maney
authors: 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.
authors: A R
authors: AR
authors: Elford
authors: 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.
authors: S R
authors: SR
authors: Hamilton
authors: Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: S
authors: S
authors: Scheu
authors: Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: K
authors: K
authors: Pfeffer
authors: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: J
authors: J
authors: Bode
authors: Institute for Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: H-W
authors: HW
authors: Mittrücker
authors: Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, Germany.
authors: M
authors: M
authors: Lohoff
authors: Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, Germany.
authors: M
authors: M
authors: Huber
authors: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: D
authors: D
authors: Häussinger
authors: 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.
authors: P S
authors: PS
authors: Ohashi
authors: 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.
authors: T W
authors: TW
authors: Mak
authors: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors: K S
authors: KS
authors: Lang
authors: Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: P A
authors: PA
authors: Lang
mesh_terms: D000818:Animals; D017209:Apoptosis; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D007156:Immunologic Memory; D050835:Interferon Regulatory Factors / Q000502:physiology*; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000099218:Interferon Regulatory Factor-4
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D050835:Interferon Regulatory Factors; D000099218:Interferon Regulatory Factor-4; C431772:Batf protein, mouse