Abstract
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.
Highlights
Marek’s disease (MD) is a highly contagious lymphoproliferative disease of chickens caused by Marek’s disease virus (MDV) or Gallid herpesvirus 2 (GaHV-2), which serves as a natural virusinduced tumor model in chickens
The roles of T lymphocytes and cytotoxic CD8 T cells as well as early cytokine expression in MD vaccine-induced protection have been extensively examined in previous studies [18,19,20,21,22,23,24,25,26, 32, 33, 41], there were a lot of gaps in the knowledge of T-cell immunity against MD [11]
[1] what are the dynamic and phenotypic changes of T cells responses in systemic and local tissues after vaccination? [2] whether, T cell subsets other than CD8 T cells respond to MD vaccination? [3] In addition to cytotoxicity, whether T cells express specific cytokines and effector molecules that may correlate with immune protection induced by MD vaccines? In the present study, we filled some of these gaps through a more comprehensive analysis of T cell responses to CVI988 vaccination by flow cytometry
Summary
Marek’s disease (MD) is a highly contagious lymphoproliferative disease of chickens caused by Marek’s disease virus (MDV) or Gallid herpesvirus 2 (GaHV-2), which serves as a natural virusinduced tumor model in chickens. This disease is characterized by neurological disorders, deadly lymphoma of CD4 T cells and immunosuppression [1]. It is crucial to dissect the immune protective mechanisms of current MD vaccines in order to develop better ones against very virulent plus MDV strains
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