反刍动物细胞介导免疫:新方法和新见解

• ¹法国国家农业、营养和环境研究所(INRAE
• ²São圣保罗大学，巴西

19世纪末，随着埃利·梅契尼科夫(Elie Metchnikoff)对吞噬作用和埃米尔·贝林(Emil Behring)和保罗·埃利希(Paul Ehrlich)对中和抗体的描述，免疫学成为一门科学学科。长期以来，这些重大发现分别奠定了先天免疫和后天免疫的基础(Kaufmann, 2019)。直到20世纪60年代初，George Mackaness团队的观察才首次证明胸腺来源的淋巴细胞(t淋巴细胞或t细胞)能够转移对感染因子的保护，从而定义了细胞介导免疫(CMI) (Wing和Remington, 1977)。从那时起，这种依赖抗原特异性t细胞而非抗体直接活动的适应性免疫，已经与多种生理过程有关，包括宿主对感染的反应、免疫耐受和对癌症的抵抗。几十年来，反刍动物t细胞的生物学一直是免疫学家感兴趣的主题，对这些细胞的研究有助于对免疫系统的主要观察(Guzman和Montoya, 2018)。然而，适应工具的缺乏，加上啮齿动物模型的主导地位，限制了反刍动物CMI的新发现的出现和该领域专家数量的扩大。为了弥补这一缺点，本研究课题报告了探索反刍动物细胞适应性免疫反应的实验策略，并在生理和病理条件的背景下为这些机制提供了新的见解。地方性牛白血病(EBL)是一种由牛白血病病毒(BLV)引起的慢性传染性疾病，它损害淋巴细胞活性，导致免疫反应功能障碍。关于EBL发病机制的研究大多集中在B淋巴细胞和t淋巴细胞机制的分析上(Schwartz and Levy, 1994)。然而，最近的观察显示，中性粒细胞作为先天免疫和适应性免疫的调节因子(Kalyan和Kabelitz, 2014)对这些细胞在EBL中的作用提出了质疑。
显示不同BLV原病毒载量的奶牛。作者证明，BLV感染以前病毒负荷依赖的方式影响中性粒细胞的免疫功能，这可能与BLV感染个体中乳腺炎等感染的较高发病率有关。Rainard等人广泛回顾了反刍动物乳腺(MG)适应性免疫反应机制的报告，重点是细胞介导免疫。乳腺具有与乳汁的生产、储存和分泌相适应的物理和细胞防御，这与暴露于入侵者的其他器官的机制不同。哺乳动物乳腺的免疫功能也有很大差异，这种特殊性限制了从一个物种到另一个物种的推断(Watson, 1980)。在此背景下，作者汇编了现有的知识，从先驱到最新的出版物，以探索反刍动物MG中细胞免疫的特异性。他们还讨论了有关乳腺免疫的主要知识差距，这些知识差距阻碍了针对乳腺内感染的有效疫苗的开发。宿主免疫反应涉及无数复杂的过程，难以在实验室条件下模拟。因此，动物模型在免疫学的不同领域仍然是必要的，包括疫苗的研发。然而，涉及动物实验的伦理和经济问题推动了对体内观察的替代方案的实施，目前已有若干体外免疫原性模型来探索免疫反应的多个功能相关部分(Hendriksen, 2009)。Davis等人描述了一个体外平台，旨在研究CD4 +和CD8 + t细胞对鸟副结核分枝杆菌和牛分枝杆菌候选疫苗的原代和回忆反应。作者还讨论了牛在开发体外模型方面的潜力，以研究病原体进化出的干扰免疫反应和引起持续性疾病的机制，从而促进获得开发新型疫苗所需的知识。树突状细胞的描述是免疫学重大发现的基石。 In the early 1990s, the emergence of protocols allowing the production monocytes-derived dendritic cells (moDC) paved the way for a better understanding of multiple processes of immune response including host response to infections and cancer, as well as immunotolerance (Cabeza-Cabrerizo et al., 2021). Although protocols for the production of bovine moDC based on the isolation of monocytes by magnetic sorting have been described (Park et al., 2016;Guzman et al., 2019), the cost and the yield of this approach can represent a handicap. As an alternative, Cunha et al. propose cost and time-efficient protocols for the production of moDC and for the study of antigen presentation in bovine. These protocols might contribute to the setup of studies involving a large number of individuals, requiring a large number of cells or relying on the utilisation of cryopreserved samples.The immune checkpoint blockade has revolutionized the therapeutic landscape in oncology. Its success in cancer therapy implies that targeting similar pathways may prove beneficial in preventing and treating infectious diseases. Indeed, persistent infections are sustained by T-cell exhaustion, which is caused by the expression of immune checkpoint molecules that limit cell-mediated protective immunity (Wykes and Lewin, 2018). In this scenario, Souza et al. explore the role of the checkpoint molecules in the transition period and their association with the uterine health. Their observations might contribute to current efforts targeting the identification of resilient dairy cows and the development of innovative (immunological) non-antibiotic approaches covering the most critical period of the cow's life.As a whole, this Research Topic proposes alternatives to some drawbacks involving the study of cell-mediated immunity in ruminants and highlights the better understanding of this arm of immune response as a fundamental step for the development of improved vaccines and therapies for these species.