Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection
Abstract Introduction Although the role of dengue virus (DENV)‐specific T cells in the pathogenesis of acute dengue infection is emerging, the functionality of virus‐specific T cells associated with milder clinical disease has not been well studied. We sought to investigate how the functionality of...
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doaj-0809ebf5295943e8b7bb78feb4d2710c2020-11-25T03:18:55ZengWileyImmunity, Inflammation and Disease2050-45272019-12-017427628510.1002/iid3.271Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infectionDulharie T. Wijeratne0Samitha Fernando1Laksiri Gomes2Chandima Jeewandara3Geethal Jayarathna4Yashoda Perera5Samurdhi Wickramanayake6Ananda Wijewickrama7Graham S. Ogg8Gathsaurie N. Malavige9Centre for Dengue Research, Faculty of Medical Sciences University of Sri Jayewardenepura Nugegoda Sri LankaCentre for Dengue Research, Faculty of Medical Sciences University of Sri Jayewardenepura Nugegoda Sri LankaCentre for Dengue Research, Faculty of Medical Sciences University of Sri Jayewardenepura Nugegoda Sri LankaCentre for Dengue Research, Faculty of Medical Sciences University of Sri Jayewardenepura Nugegoda Sri LankaCentre for Dengue Research, Faculty of Medical Sciences University of Sri Jayewardenepura Nugegoda Sri LankaCentre for Dengue Research, Faculty of Medical Sciences University of Sri Jayewardenepura Nugegoda Sri LankaCentre for Dengue Research, Faculty of Medical Sciences University of Sri Jayewardenepura Nugegoda Sri LankaInfectious Diseases Hospital Angoda Sri LankaCentre for Dengue Research, Faculty of Medical Sciences University of Sri Jayewardenepura Nugegoda Sri LankaCentre for Dengue Research, Faculty of Medical Sciences University of Sri Jayewardenepura Nugegoda Sri LankaAbstract Introduction Although the role of dengue virus (DENV)‐specific T cells in the pathogenesis of acute dengue infection is emerging, the functionality of virus‐specific T cells associated with milder clinical disease has not been well studied. We sought to investigate how the functionality of DENV–NS3 and DENV–NS5 protein‐specific T cells differ in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). Methods Using intracellular cytokine assays, we assessed the production of interferon γ (IFNγ), tumor necrosis factor‐α (TNF‐α), macrophage inflammatory protein‐1β (MIP‐1β), and CD107a expression in adult patients with acute DF (n = 21) and DHF (n = 22). Results Quadruple cytokine‐producing, polyfunctional DENV–NS3‐ and DENV–NS5‐specific T cells were more frequent in those with DF when compared to those with DHF. While DENV–NS3‐ and DENV–NS5‐specific T cells in patients with DF expressed IFNγ > TNF‐α > MIP‐β > CD107a, T cells of those with DHF predominantly expressed CD107a > MIP‐1β > IFNγ > TNF‐α. Overall production of IFNγ or TNF‐α by DENV–NS3‐ and DENV–NS5‐specific T cells was significantly higher in patients with DF. The majority of NS3‐specific T cells in patients with DF (78.6%) and DHF (68.9%) were single‐cytokine producers; 76.6% of DENV–NS5‐specific T cells in those with DF and 77.1% of those with DHF, produced only a single cytokine. However, no significant association was found with polyfunctional T‐cell responses and the degree of viraemia. Conclusions Our results suggest that the functional phenotype of DENV‐specific T cells are likely to associate with clinical disease severity.https://doi.org/10.1002/iid3.271clinical disease severitycytokinesdenguepolyfunctional T cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dulharie T. Wijeratne Samitha Fernando Laksiri Gomes Chandima Jeewandara Geethal Jayarathna Yashoda Perera Samurdhi Wickramanayake Ananda Wijewickrama Graham S. Ogg Gathsaurie N. Malavige |
spellingShingle |
Dulharie T. Wijeratne Samitha Fernando Laksiri Gomes Chandima Jeewandara Geethal Jayarathna Yashoda Perera Samurdhi Wickramanayake Ananda Wijewickrama Graham S. Ogg Gathsaurie N. Malavige Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection Immunity, Inflammation and Disease clinical disease severity cytokines dengue polyfunctional T cells |
author_facet |
Dulharie T. Wijeratne Samitha Fernando Laksiri Gomes Chandima Jeewandara Geethal Jayarathna Yashoda Perera Samurdhi Wickramanayake Ananda Wijewickrama Graham S. Ogg Gathsaurie N. Malavige |
author_sort |
Dulharie T. Wijeratne |
title |
Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection |
title_short |
Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection |
title_full |
Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection |
title_fullStr |
Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection |
title_full_unstemmed |
Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection |
title_sort |
association of dengue virus‐specific polyfunctional t‐cell responses with clinical disease severity in acute dengue infection |
publisher |
Wiley |
series |
Immunity, Inflammation and Disease |
issn |
2050-4527 |
publishDate |
2019-12-01 |
description |
Abstract Introduction Although the role of dengue virus (DENV)‐specific T cells in the pathogenesis of acute dengue infection is emerging, the functionality of virus‐specific T cells associated with milder clinical disease has not been well studied. We sought to investigate how the functionality of DENV–NS3 and DENV–NS5 protein‐specific T cells differ in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). Methods Using intracellular cytokine assays, we assessed the production of interferon γ (IFNγ), tumor necrosis factor‐α (TNF‐α), macrophage inflammatory protein‐1β (MIP‐1β), and CD107a expression in adult patients with acute DF (n = 21) and DHF (n = 22). Results Quadruple cytokine‐producing, polyfunctional DENV–NS3‐ and DENV–NS5‐specific T cells were more frequent in those with DF when compared to those with DHF. While DENV–NS3‐ and DENV–NS5‐specific T cells in patients with DF expressed IFNγ > TNF‐α > MIP‐β > CD107a, T cells of those with DHF predominantly expressed CD107a > MIP‐1β > IFNγ > TNF‐α. Overall production of IFNγ or TNF‐α by DENV–NS3‐ and DENV–NS5‐specific T cells was significantly higher in patients with DF. The majority of NS3‐specific T cells in patients with DF (78.6%) and DHF (68.9%) were single‐cytokine producers; 76.6% of DENV–NS5‐specific T cells in those with DF and 77.1% of those with DHF, produced only a single cytokine. However, no significant association was found with polyfunctional T‐cell responses and the degree of viraemia. Conclusions Our results suggest that the functional phenotype of DENV‐specific T cells are likely to associate with clinical disease severity. |
topic |
clinical disease severity cytokines dengue polyfunctional T cells |
url |
https://doi.org/10.1002/iid3.271 |
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