title: Virus-specific T lymphocytes home to the skin during natural dengue infection.
abstract: 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.
authors.affiliation: Immunology Programme, Life Sciences Institute and Department of Microbiology, National University of Singapore, Singapore 117456, Singapore. Programme in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169857, Singapore. laura.rivino@duke-nus.edu.sg.
authors.forename: Laura
authors.initials: L
authors.lastname: Rivino
authors.affiliation: Immunology Programme, Life Sciences Institute and Department of Microbiology, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Emmanuelle A
authors.initials: EA
authors.lastname: Kumaran
authors.affiliation: Institute of Infectious Diseases and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore 308433, Singapore.
authors.forename: Tun-Linn
authors.initials: TL
authors.lastname: Thein
authors.affiliation: Immunology Programme, Life Sciences Institute and Department of Microbiology, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Chien Tei
authors.initials: CT
authors.lastname: Too
authors.affiliation: Institute of Infectious Diseases and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore 308433, Singapore.
authors.forename: Victor Chih Hao
authors.initials: VC
authors.lastname: Gan
authors.affiliation: Defense Medical and Environmental Research Institute, National Laboratories, Singapore 118230, Singapore.
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Hanson
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.
authors.forename: Annelies
authors.initials: A
authors.lastname: Wilder-Smith
authors.affiliation: Programme in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169857, Singapore. Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore 117609, Singapore.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertoletti
authors.affiliation: Immunology Programme, Life Sciences Institute and Department of Microbiology, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Nicholas R J
authors.initials: NR
authors.lastname: Gascoigne
authors.affiliation: Institute of Infectious Diseases and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore 308433, Singapore.
authors.forename: David Chien
authors.initials: DC
authors.lastname: Lye
authors.affiliation: Institute of Infectious Diseases and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore 308433, Singapore. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.
authors.forename: Yee Sin
authors.initials: YS
authors.lastname: Leo
authors.affiliation: Division of Infection and Immunity, University College of London, London WC1E 6BT, UK.
authors.forename: Arne N
authors.initials: AN
authors.lastname: Akbar
authors.affiliation: Immunology Programme, Life Sciences Institute and Department of Microbiology, National University of Singapore, Singapore 117456, Singapore.
authors.forename: David M
authors.initials: DM
authors.lastname: Kemeny
authors.affiliation: Immunology Programme, Life Sciences Institute and Department of Microbiology, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacAry
mesh_terms: D000208:Acute Disease; D000998:Antiviral Agents / Q000276:immunology; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000276:immunology; D003715:Dengue / Q000276:immunology* / Q000821:virology*; D003716:Dengue Virus / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D010455:Peptides / Q000276:immunology; D010641:Phenotype; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D019595:Severe Dengue / Q000276:immunology / Q000821:virology; D012867:Skin / Q000166:cytology / Q000276:immunology*; D013045:Species Specificity
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides; D016201:Receptors, Lymphocyte Homing