扬州大学兽医学院畜禽T细胞免疫创新团队 为马立克氏病/...

hantavirus

近日，来自扬州大学兽医学院动物重要疫病与人兽共患病协同创新中心、教育部禽病预防医学重点实验室的畜禽T细胞免疫创新团队在《Cellular and Molecular Life Sciences》发表综述文章Revisiting cellular immune response to oncogenic Marek’s disease virus: the rising of avian T-cell immunity(DOI: 10.1007/s00018-020-03477-z)，为马立克氏病的T细胞免疫研究提出了新见解和新方向。


马立克氏病病毒（Marek’s disease virus，MDV）是一种高度致瘤性疱疹病毒，可引起禽类致死性的T淋巴细胞瘤（CD4+）。尽管疫苗接种已实行几十年，但是MDV的免疫保护机制并不明确。MDV野毒毒力不断向强毒进化，是否会有朝一日导致大爆发令人十分担忧。而且，由于对MDV免疫保护性相关指标不了解，新疫苗的设计、研发非常缓慢。

面上述问题，本文首先引入了哺乳动物抗病毒T细胞免疫的研究进展与理念，比较了禽细胞免疫与哺乳动物细胞免疫的差异；回顾了不同免疫细胞亚群在MDV感染或免疫中的作用及已有研究的不足，提出了有待深入研究的三大问题。
(1) MDV感染或免疫后，未被感染的免疫细胞如何参与抗MDV免疫应答；

(2) 鸡T细胞如何被激活和识别MDV抗原；

(3)激活的T细胞有何功能、特征及与免疫保护的关系。

该文还总结了可用于鸡T细胞免疫研究的方法学进展。



本文为MDV疫苗研发、禽T细胞免疫研究提供了有用的信息和新思路。对一些重大畜禽疾病（非体液免疫为主）的T细胞免疫研究也具有借鉴意义。




Figure 1. Cellular immune response to Marek’sdisease virus: a proposal. After inhalation of cell-free virus particle,macrophages and DCs are infected. MDV-infected macrophages transmit the virusto B cells and T cells via cell-cell contact, eventually leading to CD4 T celltransformation and lymphoma. While macrophages, NK cells and high percentage of γδ T cells participate in the first-line host defense, infected or uninfectedadjacent antigen-presenting cells present MDV antigen to CD4 and CD8 T cells throughclassical antigen presentation or cross-presentation, leading to T cellsactivation and differentiation. However, which epitope or MDV antigen arepresented and recognized by T cells has not been identified. Activated CD8 Tcells play a critical role in the protection against MD tumor but theireffector functions are not fully addressed. Activated CD4 T cells maydifferentiate into effector T cells and distinct T helper subsets such as Th1,Th2, Th17, Treg and so on. While TGF-β+Tregs were shown to contributeto immunosuppression induced by MDV, whether other helper T cells exist afterMDV infection or vaccination and how they function in anti-MDV immunity havenot been studied. Although effector molecules and cytokines including IFN-γ,TNF-α, IL-2, granzymes, perforin, IL-17, IL-12 and IL-18 were detected at mRNA level after vaccination, by which immune cell subset they are produced has notbeen examined at single cell level or protein level. To answer theabove-mentioned questions relies on the advances of methods for studyingcellular immunity and availability of immunological reagents in chickens.


青年教师杨奕博士为论文第一作者，该校引进人才“江苏特聘教授”商绍彬教授和秦爱建教授为论文共同通讯作者。该成果得到国家自然科学基金（31972717）、江苏省青年基金、中国博士后科学基金等项目的资助。



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. Although Marek’s disease (MD) is well controlled by current vaccines, the evolution of MDV field viruses towards increasing virulence is concerning as a better vaccine to combat very virulent plus MDV is still lacking. Our understanding of molecular and cellular immunity to MDV and its immunopathogenesis has significantly improved, but those findings about cellular immunity to MDV are largely out-of-date, hampering the development of more effective vaccines against MD. T cell-mediated cellular immunity was thought to be of paramount importance against MDV. However, MDV also infects macrophages, B cells and T cells, leading to immunosuppression and T cell lymphoma. Additionally, there is limited information about how uninfected immune cells respond to MDV infection or vaccination, specifically, the mechanisms by which T cells are activated and recognize MDV antigens and how the function and properties of activated T cells correlate with immune protection against MDV or MD tumor. The current review revisits the roles of each immune cell subset and its effector mechanisms in the host immune response to MDV infection or vaccination from the point of view of comparative immunology. We particularly emphasize areas of research requiring further investigation and provide useful information for rational design and development of novel MDV vaccines.



原文链接
https://link.springer.com/article/10.1007/s00018-020-03477-z

https://rdcu.be/b1ZE7