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

• 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: Article
• Language: English
• Published: 2016
• Subjects: Medicine
• Online Access: https://hdl.handle.net/10356/82909; http://hdl.handle.net/10220/40388
• Institution: Nanyang Technological University

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.