Cellular immunology of sequential dengue virus infection and its role in disease pathogenesis

The increased risk for severe dengue disease during secondary dengue virus (DENV) infections, along with the clinical and pathological evidence pointing to cytokines as the proximal mediators of disease, has interested cellular immunologists in exploring the role of DENV-specific T lymphocytes in the pathogenesis of dengue-associated plasma leakage. Recent technological advances in the analysis of virus-specific T cells, applied to blood samples collected before, during and after acute DENV infections, have demonstrated that memory DENV-specific T cells from a prior infection respond with altered cytokine production to heterologous DENV serotypes and that the level of activation and expansion of these memory cells during acute DENV infection correlates with disease severity. Limited data suggest that specific T cell response profiles may predict a higher risk for severe disease during secondary infection. Application of these techniques and principles to animal models and to clinical trials may advance the development of novel therapeutics and protective vaccines.