Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 7, Issue 278, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aaa0526
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Funding
- National Research Foundation [National University of Singapore (NUS)-Hebrew University of Jerusalem-Campus for Research Excellence and Technological Enterprise] [R182-005-172-281]
- National Research Foundation [NUS Office of the Deputy President (Research and Technology)] [R182-000-192-133]
- National Research Foundation [National Medical Research Council (NMRC): STOP-Dengue Translational and Clinical Research grant] [R-182-003-220-275]
- [NMRC/STaR/013/2012]
- BBSRC [BB/L025302/1, BB/G530433/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/L025302/1, BB/G530433/1] Funding Source: researchfish
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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.
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