Research ArticleDengue

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

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Science Translational Medicine  11 Mar 2015:
Vol. 7, Issue 278, pp. 278ra35
DOI: 10.1126/scitranslmed.aaa0526

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Getting under dengue virus’s skin

Dengue virus infection is transmitted by mosquitoes, suggesting that a vaccine targeting the immune response to the skin could have protective effects. Rivino et al. examined individuals with natural dengue infection to determine whether skin-mediated immunity indeed contributes to the fight against dengue. They found that dengue infection induced highly activated CD8+ T cells that express the skin-homing marker cutaneous lymphocyte-associated antigen (CLA). CLA expression by these cells correlated with their ability to traffic to the skin during dengue infection. Notably, CLA was not up-regulated in bystander HCMV-restricted cells in these individuals, suggesting that the skin-targeted homing is pathogen-specific. These data support a role for skin-directed immunosurveillance against dengue and reinforce a skin-targeted vaccine strategy for this virus.


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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