IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection
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- David G. Brooks
- Department of Microbiology, Immunology and Molecular Genetics, and the UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles CA 90095;
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- Sang-Jun Ha
- Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;
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- Heidi Elsaesser
- Viral-Immunobiology Laboratory, Department of Immunology and Microbial Sciences and Department of Infectology, The Scripps Research Institute. San Diego, CA 92037;
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- Arlene H. Sharpe
- Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115; and
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- Gordon J. Freeman
- Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115
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- Michael B. A. Oldstone
- Viral-Immunobiology Laboratory, Department of Immunology and Microbial Sciences and Department of Infectology, The Scripps Research Institute. San Diego, CA 92037;
書誌事項
- 公開日
- 2008-12-23
- DOI
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- 10.1073/pnas.0811139106
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p>Suppression of T-cell responses by host-derived regulatory factors is a key event leading to viral persistence. Antibody blockade of either IL-10 or programmed death-ligand 1 (PD-L1) during viral persistence enhances T-cell function and reduces viral titers. Because blockade of these immunoregulatory networks represents a powerful approach to establish immune control during persistent infection, it is important to determine whether these immunoinhibitory factors act independently or jointly and if combined blockade of these factors further enhances T-cell immunity and viral clearance. Herein, we demonstrate that the IL-10 and PD-L1 immunosuppressive pathways are mechanistically distinct. As a result, simultaneous blockade of IL-10 and PD-L1 was significantly more effective in restoring antiviral T-cell responses than blockade of either alone, and led to substantially enhanced control of an established persistent viral infection. Thus, combinatorial blockade of multiple immune-regulatory molecules may ultimately restore the T-cell responses required to tip the balance from viral persistence to immune-mediated control or elimination of persistent infection.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 105 (51), 20428-20433, 2008-12-23
Proceedings of the National Academy of Sciences