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.
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 DVnon-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: Marjo M P C Donners; Ine M J Wolfs; Servé Olieslagers; Zeynab Mohammadi-Motahhari; Vadim Tchaikovski; Sylvia Heeneman; Jaap D van Buul; Vincenza Caolo; Daniël G M Molin; Mark J Post; Johannes Waltenberger Journal: Arterioscler Thromb Vasc Biol Date: 2010-09-02 Impact factor: 8.311
Authors: H Gille; J Kowalski; B Li; J LeCouter; B Moffat; T F Zioncheck; N Pelletier; N Ferrara Journal: J Biol Chem Date: 2000-10-31 Impact factor: 5.157
Authors: Meta Michels; André J A M van der Ven; Kis Djamiatun; Rob Fijnheer; Philip G de Groot; Arjan W Griffioen; Silvie Sebastian; Sultana M H Faradz; Quirijn de Mast Journal: Am J Trop Med Hyg Date: 2012-09-04 Impact factor: 2.345