Activation of dengue virus-specific T cells modulates vascular endothelial growth factor receptor 2 expression

作者：Rattanamahaphoom Jittra****; Leaungwutiwong Pornsawan; Limkittikul Kriengsak; Kosoltanapiwat Nathamon; Srikaitkhachorn Anon^*

来源：Asian Pacific Journal of Allergy and Immunology, 2017, 35(3): 171-178.

DOI：10.12932/AP0810

• Dengue hemorrhagic fever
• vascular leakage
• vascular permeability
• vascular endothelial growth factor receptor 2
• T cells

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 DHE 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.
Method: 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.

• 出版日期2017-9