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.
Dung
Nguyen Thi Phuong
NT
Oxford University Clinical Research Unit and Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Duyen
Huynh Thi Le
HT
Thuy
Nguyen Thi Van
NT
Ngoc
Tran Van
TV
Chau
Nguyen Van Vinh
NV
Hien
Tran Tinh
TT
Rowland-Jones
Sarah L
SL
Dong
Tao
T
Farrar
Jeremy
J
Wills
Bridget
B
Simmons
Cameron P
CP
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
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