Timing of CD8+ T Cell Responses in Relation to Commencement of Capillary Leakage in Children with Dengue
Nguyen Thi Phuong Dunga b, Huynh Thi Le Duyena b, Nguyen Thi Van Thuya b, Tran Van Ngocc d, Nguyễn Văn Vĩnh Châuc d, Tran Tinh Hienc d, Sarah Rowland‐Jonese f, Tao Donge f, Jeremy Farrara b g h✉, Bridget A. Willsa b g h✉, Cameron Paul Simmonsa b g h
- aOxford University Clinical Research Unit
- b*Oxford University Clinical Research Unit and
- cHospital for Tropical Diseases, Ho Chi Minh City
- d†Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
- eMedical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital
- f‡Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital; and
- gNuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford , Oxford
- h§Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford, Oxford, United Kingdom
- ✉Corresponding author
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Abstract
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.
TL;DRThe temporal mismatch between the appearance of measurable surface activated or NS3133–142-specific CD8+ T cells suggests that these cells are sequestered at sites of infection, have phenotypes not detected by the approach, or that other mechanisms independent of CD8- T cells are responsible for early triggering of capillary leakage in children with DHF. (Semantic Scholar)