An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens

Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. The most efficacious vaccine, CVI988/Rispens (CVI988), against MD has been used for several decades. However, the mechanisms lead...

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Main Authors: Xiaoli Hao, Shuai Li, Jiaqi Li, Yi Yang, Aijian Qin, Shaobin Shang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.645426/full
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author Xiaoli Hao
Xiaoli Hao
Xiaoli Hao
Shuai Li
Jiaqi Li
Yi Yang
Yi Yang
Yi Yang
Aijian Qin
Aijian Qin
Aijian Qin
Aijian Qin
Shaobin Shang
Shaobin Shang
Shaobin Shang
Shaobin Shang
author_facet Xiaoli Hao
Xiaoli Hao
Xiaoli Hao
Shuai Li
Jiaqi Li
Yi Yang
Yi Yang
Yi Yang
Aijian Qin
Aijian Qin
Aijian Qin
Aijian Qin
Shaobin Shang
Shaobin Shang
Shaobin Shang
Shaobin Shang
author_sort Xiaoli Hao
collection DOAJ
description Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. The most efficacious vaccine, CVI988/Rispens (CVI988), against MD has been used for several decades. However, the mechanisms leading to protective immunity following vaccination are not fully understood. In this study, employing multi-parameter flow cytometry, we performed a comprehensive analysis of T cell responses in CVI988-vaccinated chickens. CVI988 vaccination induced significant expansion of γδ T cells and CD8α+ T cells but not CD4+ T cells in spleen, lung and blood at early time-points. The expansion of these cells was CVI988-specific as infection with very virulent MDV RB1B did not elicit expansion of either γδ or CD8α+ T cells. Phenotypic analysis showed that CVI988 vaccination elicited preferential proliferation of CD8α+ γδ T cells and CD8αα co-receptor expression was upregulated on γδ T cells and CD8α+ T cells after immunization. Additionally, cell sorting and quantitative RT-PCR showed that CVI988 vaccination activated γδ T cells and CD8α+ T cells which exhibited differential expression of cytotoxic and T cell-related cytokines. Lastly, secondary immunization with CVI988 induced the expansion of CD8+ T cells but not γδ T cells at higher magnitude, compared to primary immunization, suggesting CVI988 did induce memory CD8+ T cells but not γδ T cells in chickens. Our results, for the first time, reveal a potential role of γδ T cells in CVI988-induced immune protection and provide new insights into the mechanism of immune protection against oncogenic MDV.
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spelling doaj.art-648bfaa3797d40caa25b70a945b69f2e2022-12-21T19:04:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011210.3389/fimmu.2021.645426645426An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in ChickensXiaoli Hao0Xiaoli Hao1Xiaoli Hao2Shuai Li3Jiaqi Li4Yi Yang5Yi Yang6Yi Yang7Aijian Qin8Aijian Qin9Aijian Qin10Aijian Qin11Shaobin Shang12Shaobin Shang13Shaobin Shang14Shaobin Shang15College of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaInstitute of Comparative Medicine, Yangzhou University, Yangzhou, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaInstitute of Comparative Medicine, Yangzhou University, Yangzhou, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, ChinaInternational Corporation Laboratory of Agriculture and Agricultural Products Safety, Yangzhou University, Yangzhou, ChinaMinistry of Education Key Laboratory for Avian Preventive Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaInstitute of Comparative Medicine, Yangzhou University, Yangzhou, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, ChinaInternational Corporation Laboratory of Agriculture and Agricultural Products Safety, Yangzhou University, Yangzhou, ChinaMarek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. The most efficacious vaccine, CVI988/Rispens (CVI988), against MD has been used for several decades. However, the mechanisms leading to protective immunity following vaccination are not fully understood. In this study, employing multi-parameter flow cytometry, we performed a comprehensive analysis of T cell responses in CVI988-vaccinated chickens. CVI988 vaccination induced significant expansion of γδ T cells and CD8α+ T cells but not CD4+ T cells in spleen, lung and blood at early time-points. The expansion of these cells was CVI988-specific as infection with very virulent MDV RB1B did not elicit expansion of either γδ or CD8α+ T cells. Phenotypic analysis showed that CVI988 vaccination elicited preferential proliferation of CD8α+ γδ T cells and CD8αα co-receptor expression was upregulated on γδ T cells and CD8α+ T cells after immunization. Additionally, cell sorting and quantitative RT-PCR showed that CVI988 vaccination activated γδ T cells and CD8α+ T cells which exhibited differential expression of cytotoxic and T cell-related cytokines. Lastly, secondary immunization with CVI988 induced the expansion of CD8+ T cells but not γδ T cells at higher magnitude, compared to primary immunization, suggesting CVI988 did induce memory CD8+ T cells but not γδ T cells in chickens. Our results, for the first time, reveal a potential role of γδ T cells in CVI988-induced immune protection and provide new insights into the mechanism of immune protection against oncogenic MDV.https://www.frontiersin.org/articles/10.3389/fimmu.2021.645426/fullγδ T cellCD8 T cellimmune responseMDVvaccine
spellingShingle Xiaoli Hao
Xiaoli Hao
Xiaoli Hao
Shuai Li
Jiaqi Li
Yi Yang
Yi Yang
Yi Yang
Aijian Qin
Aijian Qin
Aijian Qin
Aijian Qin
Shaobin Shang
Shaobin Shang
Shaobin Shang
Shaobin Shang
An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens
Frontiers in Immunology
γδ T cell
CD8 T cell
immune response
MDV
vaccine
title An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens
title_full An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens
title_fullStr An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens
title_full_unstemmed An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens
title_short An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens
title_sort anti tumor vaccine against marek s disease virus induces differential activation and memory response of γδ t cells and cd8 t cells in chickens
topic γδ T cell
CD8 T cell
immune response
MDV
vaccine
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.645426/full
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