title: Activation of dengue virus-specific T cells modulates vascular endothelial growth factor receptor 2 expression.
abstract: BACKGROUND
  The pathogenic mechanisms underlying the increased vascular permeability in dengue hemorrhagic fever (DHF) are not well understood. Enhanced cellular immune activation, especially activation of serotype-cross reactive T cells, has been implicated in plasma leakage in DHF. Changes in several biological markers and mediators including cytokines, chemokines, angiogenic factors and their receptors have been shown to correlate with disease severity. A decline in plasma levels of a soluble form of vascular endothelial growth factor receptor 2 (VEGFR2), a receptor of vascular endothelial growth factor (VEGF), has been associated with plasma leakage in dengue patients.
  
  
  OBJECTIVE
  We aimed to investigate the effect of dengue virus (DV)-specific CD8⁺ T cells on the expression of VEGFR2 on endothelial cells.
  
  
  METHODS
  An in vitro model was developed in which dengue virus-specific CD8⁺ T cells generated from peripheral blood mononuclear cells (PBMCs) of DHF patients were co-cultured with antigen-presenting cells, human umbilical vein endothelial cells (HUVECs) and activated with DV non-structural protein 3 (NS3) peptides. The expression of VEGFR2 by endothelial cells was measured.
  
  
  RESULTS
  DV-specific CD8⁺ T cells were serotype cross-reactive. Activation of DV-specific CD8⁺ T cells resulted in down-regulation of soluble VEGFR2 production and an up-regulation of cell-associated VEGFR2.
  
  
  CONCLUSIONS
  Our findings indicate that activation of DV-specific T cell is associated with modulation of VEGFR2 expression that may contribute to increased VEGF responsiveness and vascular permeability.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Jittraporn
authors.initials: J
authors.lastname: Rattanamahaphoom
authors.affiliation: Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Pornsawan
authors.initials: P
authors.lastname: Leaungwutiwong
authors.affiliation: Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Kriengsak
authors.initials: K
authors.lastname: Limkittikul
authors.affiliation: Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Nathamon
authors.initials: N
authors.lastname: Kosoltanapiwat
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island, U.S.A.
authors.forename: Anon
authors.initials: A
authors.lastname: Srikaitkhachorn
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D003715:Dengue / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2