A Population of CD4<sup>+</sup>CD8<sup>+</sup> Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection
According to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher morbidity and mortality. We report that the frequency...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/1/90 |
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| author | Esther Dawen Yu Hao Wang Ricardo da Silva Antunes Yuan Tian Rashmi Tippalagama Shakila U. Alahakoon Gayani Premawansa Ananda Wijewickrama Sunil Premawansa Aruna Dharshan De Silva April Frazier Alba Grifoni Alessandro Sette Daniela Weiskopf |
| author_facet | Esther Dawen Yu Hao Wang Ricardo da Silva Antunes Yuan Tian Rashmi Tippalagama Shakila U. Alahakoon Gayani Premawansa Ananda Wijewickrama Sunil Premawansa Aruna Dharshan De Silva April Frazier Alba Grifoni Alessandro Sette Daniela Weiskopf |
| author_sort | Esther Dawen Yu |
| collection | DOAJ |
| description | According to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4<sup>+</sup>CD8<sup>+</sup> double-positive (DP) T cells is significantly increased in patients at risk of developing plasma leakage. Transcriptomic analysis demonstrated that CD4<sup>+</sup>CD8<sup>+</sup> DP cells were distinct from CD4<sup>+</sup> Single Positive (SP) T cells but co-clustered with CD8<sup>+</sup> SP cells, indicating a largely similar transcriptional profile. Twenty significant differentially expressed (DE) genes were identified between CD4<sup>+</sup>CD8<sup>+</sup> DP and CD8<sup>+</sup> SP cells. These genes encode OX40 and CCR4 proteins as well as other molecules associated with cell signaling on the cell surface (<i>NT5E</i>, <i>MXRA8</i>, and <i>PTPRK</i>). While comparing the profile of gene expression in CD4<sup>+</sup>CD8<sup>+</sup> DP cells from patients with and without warning signs of plasma leakage, similar expression profile was observed, implying a role of CD4<sup>+</sup>CD8<sup>+</sup> DP cells in plasma leakage through a quantitative increase rather than functional alteration. This study provided novel insight into the host immune response during the acute febrile phase of DENV infection and the role of CD4<sup>+</sup>CD8<sup>+</sup> DP T cells in the pathogenesis of plasma leakage. |
| first_indexed | 2024-03-10T00:21:33Z |
| format | Article |
| id | doaj.art-2aa09aaf330e456cb700ca96be88e23a |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T00:21:33Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-2aa09aaf330e456cb700ca96be88e23a2023-11-23T15:42:02ZengMDPI AGViruses1999-49152022-01-011419010.3390/v14010090A Population of CD4<sup>+</sup>CD8<sup>+</sup> Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral InfectionEsther Dawen Yu0Hao Wang1Ricardo da Silva Antunes2Yuan Tian3Rashmi Tippalagama4Shakila U. Alahakoon5Gayani Premawansa6Ananda Wijewickrama7Sunil Premawansa8Aruna Dharshan De Silva9April Frazier10Alba Grifoni11Alessandro Sette12Daniela Weiskopf13Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USASchool of Medicine, University of California San Diego, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USAGenetech Research Institute, Colombo 00800, Sri LankaColombo North Teaching Hospital, Ragama 11010, Sri LankaNational Institute of Infectious Diseases, Angoda 10620, Sri LankaDepartment of Zoology and Environment Sciences, University of Colombo, Colombo 00700, Sri LankaCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USAAccording to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4<sup>+</sup>CD8<sup>+</sup> double-positive (DP) T cells is significantly increased in patients at risk of developing plasma leakage. Transcriptomic analysis demonstrated that CD4<sup>+</sup>CD8<sup>+</sup> DP cells were distinct from CD4<sup>+</sup> Single Positive (SP) T cells but co-clustered with CD8<sup>+</sup> SP cells, indicating a largely similar transcriptional profile. Twenty significant differentially expressed (DE) genes were identified between CD4<sup>+</sup>CD8<sup>+</sup> DP and CD8<sup>+</sup> SP cells. These genes encode OX40 and CCR4 proteins as well as other molecules associated with cell signaling on the cell surface (<i>NT5E</i>, <i>MXRA8</i>, and <i>PTPRK</i>). While comparing the profile of gene expression in CD4<sup>+</sup>CD8<sup>+</sup> DP cells from patients with and without warning signs of plasma leakage, similar expression profile was observed, implying a role of CD4<sup>+</sup>CD8<sup>+</sup> DP cells in plasma leakage through a quantitative increase rather than functional alteration. This study provided novel insight into the host immune response during the acute febrile phase of DENV infection and the role of CD4<sup>+</sup>CD8<sup>+</sup> DP T cells in the pathogenesis of plasma leakage.https://www.mdpi.com/1999-4915/14/1/90CD4<sup>+</sup>CD8<sup>+</sup>double positiveT cellsinfectious diseasesdengue |
| spellingShingle | Esther Dawen Yu Hao Wang Ricardo da Silva Antunes Yuan Tian Rashmi Tippalagama Shakila U. Alahakoon Gayani Premawansa Ananda Wijewickrama Sunil Premawansa Aruna Dharshan De Silva April Frazier Alba Grifoni Alessandro Sette Daniela Weiskopf A Population of CD4<sup>+</sup>CD8<sup>+</sup> Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection Viruses CD4<sup>+</sup> CD8<sup>+</sup> double positive T cells infectious diseases dengue |
| title | A Population of CD4<sup>+</sup>CD8<sup>+</sup> Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection |
| title_full | A Population of CD4<sup>+</sup>CD8<sup>+</sup> Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection |
| title_fullStr | A Population of CD4<sup>+</sup>CD8<sup>+</sup> Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection |
| title_full_unstemmed | A Population of CD4<sup>+</sup>CD8<sup>+</sup> Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection |
| title_short | A Population of CD4<sup>+</sup>CD8<sup>+</sup> Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection |
| title_sort | population of cd4 sup sup cd8 sup sup double positive t cells associated with risk of plasma leakage in dengue viral infection |
| topic | CD4<sup>+</sup> CD8<sup>+</sup> double positive T cells infectious diseases dengue |
| url | https://www.mdpi.com/1999-4915/14/1/90 |
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