1. IRF4 and BATF are critical for CD8(+) T-cell function following infection with LCMV
- Author
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Haifeng C. Xu, Alisha R. Elford, Philipp A. Lang, Dieter Häussinger, Michael Lohoff, David R. McIlwain, Aleksandra A. Pandyra, Tak W. Mak, D E Speiser, Stefanie Scheu, Sathish Kumar Maney, Melanie Grusdat, Magdalena Huber, Karl S. Lang, Elisabeth Lang, Vitaly I. Pozdeev, Sarah Q. Crome, Celine Robert-Tissot, Regine J. Dress, H-W Mittrücker, J Knievel, Pamela S. Ohashi, Johannes G. Bode, Sara R. Hamilton, and Klaus Pfeffer
- Subjects
Cytotoxicity, Immunologic ,Medizin ,Apoptosis ,Biology ,CD8-Positive T-Lymphocytes ,BATF ,Lymphocytic choriomeningitis ,Lymphocyte Activation ,CD8+ T cells ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,IRF4 ,Immunopathology ,medicine ,Cytotoxic T cell ,Animals ,Lymphocytic choriomeningitis virus ,immunopathology ,hepatitis ,LCMV ,Molecular Biology ,Cells, Cultured ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Original Paper ,Cell Biology ,medicine.disease ,Virology ,3. Good health ,Mice, Inbred C57BL ,Basic-Leucine Zipper Transcription Factors ,030220 oncology & carcinogenesis ,Immunology ,Interferon Regulatory Factors ,Immunologic Memory ,CD8 - 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.Cell Death and Differentiation advance online publication 14 February 2014; doi:10.1038/cdd.2014.19.
- Published
- 2014
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