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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.

Original publication

DOI

10.1126/scitranslmed.aaa0526

Type

Journal

Science translational medicine

Publication Date

03/2015

Volume

7

Addresses

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.

Keywords

CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Skin, Humans, Cytomegalovirus, Dengue Virus, Dengue, Acute Disease, Peptides, Receptors, Lymphocyte Homing, HLA-A2 Antigen, Antiviral Agents, Lymphocyte Activation, Cell Differentiation, Cell Proliferation, Cell Movement, Species Specificity, Phenotype, Severe Dengue, Biomarkers