Virus-specific T lymphocytes home to the skin during natural dengue infection

Dengue, which is the most prevalent mosquito-borne viral disease afflicting human populations, causes a spectrum of clinical symptoms that include fever, muscle and joint pain, maculopapular skin rash, and hemorrhagic manifestations. Patients infected with dengue develop a broad antigen-specific T l...

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Main Authors: Rivino, Laura, Kumaran, Emmanuelle A., Thein, Tun-Linn, Too, Chien Tei, Gan, Victor Chih Hao, Hanson, Brendon J., Wilder-Smith, Annelies, Bertoletti, Antonio, Gascoigne, Nicholas R. J., Lye, David Chien, Leo, Yee Sin, Akbar, Arne N., Kemeny, David M., MacAry, Paul A.
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Journal Article
Language:English
Published: 2016
Subjects:
Online Access:https://hdl.handle.net/10356/82909
http://hdl.handle.net/10220/40388
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author Rivino, Laura
Kumaran, Emmanuelle A.
Thein, Tun-Linn
Too, Chien Tei
Gan, Victor Chih Hao
Hanson, Brendon J.
Wilder-Smith, Annelies
Bertoletti, Antonio
Gascoigne, Nicholas R. J.
Lye, David Chien
Leo, Yee Sin
Akbar, Arne N.
Kemeny, David M.
MacAry, Paul A.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Rivino, Laura
Kumaran, Emmanuelle A.
Thein, Tun-Linn
Too, Chien Tei
Gan, Victor Chih Hao
Hanson, Brendon J.
Wilder-Smith, Annelies
Bertoletti, Antonio
Gascoigne, Nicholas R. J.
Lye, David Chien
Leo, Yee Sin
Akbar, Arne N.
Kemeny, David M.
MacAry, Paul A.
author_sort Rivino, Laura
collection NTU
description Dengue, which is the most prevalent mosquito-borne viral disease afflicting human populations, causes a spectrum of clinical symptoms that include fever, muscle and joint pain, maculopapular skin rash, and hemorrhagic manifestations. Patients infected with dengue develop a broad antigen-specific T lymphocyte response, but the phenotype and functional properties of these cells are only partially understood. We show that natural infection induces dengue-specific CD8+ T lymphocytes that are highly activated and proliferating, exhibit antiviral effector functions, and express CXCR3, CCR5, and the skin-homing marker cutaneous lymphocyte-associated antigen (CLA). In the same patients, bystander human cytomegalovirus –specific CD8+ T cells are also activated during acute dengue infection but do not express the same tissue-homing phenotype. We show that CLA expression by circulating dengue-specific CD4+ and CD8+ T cells correlates with their in vivo ability to traffic to the skin during dengue infection. The juxtaposition of dengue-specific T cells with virus-permissive cell types at sites of possible dengue exposure represents a previously uncharacterized form of immune surveillance for this virus. These findings suggest that vaccination strategies may need to induce dengue-specific T cells with similar homing properties to provide durable protection against dengue viruses.
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spelling ntu-10356/829092020-11-01T05:31:02Z Virus-specific T lymphocytes home to the skin during natural dengue infection Rivino, Laura Kumaran, Emmanuelle A. Thein, Tun-Linn Too, Chien Tei Gan, Victor Chih Hao Hanson, Brendon J. Wilder-Smith, Annelies Bertoletti, Antonio Gascoigne, Nicholas R. J. Lye, David Chien Leo, Yee Sin Akbar, Arne N. Kemeny, David M. MacAry, Paul A. Lee Kong Chian School of Medicine (LKCMedicine) Medicine Dengue, which is the most prevalent mosquito-borne viral disease afflicting human populations, causes a spectrum of clinical symptoms that include fever, muscle and joint pain, maculopapular skin rash, and hemorrhagic manifestations. Patients infected with dengue develop a broad antigen-specific T lymphocyte response, but the phenotype and functional properties of these cells are only partially understood. We show that natural infection induces dengue-specific CD8+ T lymphocytes that are highly activated and proliferating, exhibit antiviral effector functions, and express CXCR3, CCR5, and the skin-homing marker cutaneous lymphocyte-associated antigen (CLA). In the same patients, bystander human cytomegalovirus –specific CD8+ T cells are also activated during acute dengue infection but do not express the same tissue-homing phenotype. We show that CLA expression by circulating dengue-specific CD4+ and CD8+ T cells correlates with their in vivo ability to traffic to the skin during dengue infection. The juxtaposition of dengue-specific T cells with virus-permissive cell types at sites of possible dengue exposure represents a previously uncharacterized form of immune surveillance for this virus. These findings suggest that vaccination strategies may need to induce dengue-specific T cells with similar homing properties to provide durable protection against dengue viruses. ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version 2016-04-08T03:23:54Z 2019-12-06T15:08:03Z 2016-04-08T03:23:54Z 2019-12-06T15:08:03Z 2015 Journal Article Rivino, L., Kumaran, E. A., Thein, T. L., Too, C. T., Gan, V. C. H., Hanson, B. J., et al. (2015). Virus-specific T lymphocytes home to the skin during natural dengue infection. Science Translational Medicine, 7(278), 278ra35-. 1946-6234 https://hdl.handle.net/10356/82909 http://hdl.handle.net/10220/40388 10.1126/scitranslmed.aaa0526 en Science Translational Medicine © 2015 American Association for the Advancement of Science. This is the author created version of a work that has been peer reviewed and accepted for publication by Science Translational Medicine, American Association for the Advancement of Science. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1126/scitranslmed.aaa0526]. 11 p. application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf
spellingShingle Medicine
Rivino, Laura
Kumaran, Emmanuelle A.
Thein, Tun-Linn
Too, Chien Tei
Gan, Victor Chih Hao
Hanson, Brendon J.
Wilder-Smith, Annelies
Bertoletti, Antonio
Gascoigne, Nicholas R. J.
Lye, David Chien
Leo, Yee Sin
Akbar, Arne N.
Kemeny, David M.
MacAry, Paul A.
Virus-specific T lymphocytes home to the skin during natural dengue infection
title Virus-specific T lymphocytes home to the skin during natural dengue infection
title_full Virus-specific T lymphocytes home to the skin during natural dengue infection
title_fullStr Virus-specific T lymphocytes home to the skin during natural dengue infection
title_full_unstemmed Virus-specific T lymphocytes home to the skin during natural dengue infection
title_short Virus-specific T lymphocytes home to the skin during natural dengue infection
title_sort virus specific t lymphocytes home to the skin during natural dengue infection
topic Medicine
url https://hdl.handle.net/10356/82909
http://hdl.handle.net/10220/40388
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