title: Timing of CD8+ T cell responses in relation to commencement of capillary leakage in children with dengue.
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.
authors.affiliation: Oxford University Clinical Research Unit and Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Thi Phuong
authors.initials: NT
authors.lastname: Dung
authors.forename: Huynh Thi Le
authors.initials: HT
authors.lastname: Duyen
authors.forename: Nguyen Thi Van
authors.initials: NT
authors.lastname: Thuy
authors.forename: Tran Van
authors.initials: TV
authors.lastname: Ngoc
authors.forename: Nguyen Van Vinh
authors.initials: NV
authors.lastname: Chau
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Bridget
authors.initials: B
authors.lastname: Wills
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
mesh_terms: D000293:Adolescent; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002199:Capillary Permeability / Q000276:immunology*; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D020365:RNA Helicases / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000276:immunology; D019595:Severe Dengue / Q000276:immunology* / Q000473:pathology; D017361:Viral Nonstructural Proteins / Q000276:immunology; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D015395:Histocompatibility Antigens Class I; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases