Understanding the Human T Cell Response to Dengue Virus

Our understanding of how T cells respond to dengue virus has greatly advanced in the last decade but important questions still remain unanswered. Dengue virus infection elicits a broad anti-viral T cell response with NS3, NS4b and NS5 being the main targets for CD8+ T cells, which dominate the response while the structural proteins capsid, envelope and the secreted protein NS1 are the preferential targets for CD4+ T cells. Upon T cell activation during acute dengue infection, dengue-specific T cells acquire expression of the skin-homing marker cutaneous associated antigen (CLA) and they can be found at high frequencies in the skin of infected patients. This suggests that the skin represents an important site for the immuno surveillance of dengue virus. The immunoprotective role of skin-homing dengue-specific T cells, their potential involvement in pathological skin manifestations and their long-term persistence as tissue resident T cells to provide immediate onsite protection are open questions that we are currently investigating. The contribution of pre-existing dengue-specific T cells towards protective immunity and/or immunopathology during secondary dengue infection remains a major knowledge gap. The evidence supporting these opposing outcomes and our current understanding of the characteristics of the human T cell response to dengue virus will be discussed.