Timing of CD8+ T Cell Responses in Relation to Commencement of Capillary Leakage in Children with Dengue

Immune activation is a feature of dengue hemorrhagic fever (DHF) and CD8(+) T cell responses in particular have been suggested as having a role in the vasculopathy that characterizes this disease. By phenotyping CD8(+) T cells (CD38(+)/HLA-DR+, CD38(+)/Ki-67(+), or HLA-DR+/Ki-67(+)) in serial blood samples from children with dengue, we found no evidence of increased CD8(+) T cell activation prior to the commencement of resolution of viremia or hemoconcentration. Investigations with MHC class I tetramers to detect NS3(133-142)-specific CD8(+) T cells in two independent cohorts of children suggested the commencement of hemoconcentration and thrombocytopenia in DHF patients generally begins before the appearance of measurable frequencies of NS3(133-142)-specific CD8(+) T cells. The temporal mismatch between the appearance of measurable surface activated or NS3(133-142)-specific CD8(+) T cells suggests that these cells are sequestered at sites of infection, have phenotypes not detected by our approach, or that other mechanisms independent of CD8(+) T cells are responsible for early triggering of capillary leakage in children with DHF. The Journal of Immunology, 2010, 184: 7281-7287.