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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





Science translational medicine

Publication Date





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.


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