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

Autor: Grusdat M; Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany., McIlwain DR; Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany., Xu HC; 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., Pozdeev VI; Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany., Knievel J; Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany., Crome SQ; 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., Robert-Tissot C; 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., Dress RJ; Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany., Pandyra AA; Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany., Speiser DE; 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., Lang E; Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany., Maney SK; Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany., Elford AR; 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., Hamilton SR; 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., Scheu S; Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany., Pfeffer K; Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany., Bode J; Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany., Mittrücker HW; Institute for Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Lohoff M; Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, Germany., Huber M; Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, Germany., Häussinger D; Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany., Ohashi PS; 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., Mak TW; 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., Lang KS; Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany., Lang PA; Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
Jazyk: angličtina
Zdroj: Cell death and differentiation [Cell Death Differ] 2014 Jul; Vol. 21 (7), pp. 1050-60. Date of Electronic Publication: 2014 Feb 14.
DOI: 10.1038/cdd.2014.19
Abstrakt: 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.
Databáze: MEDLINE
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