Lang Haeree P, Osum Kevin C, Friedenberg Steven G
Center for Immunology, University of Minnesota, Minneapolis, MN 55414, USA; Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.
Center for Immunology, University of Minnesota, Minneapolis, MN 55414, USA.
Vet Immunol Immunopathol. 2024 Sep;275:110816. doi: 10.1016/j.vetimm.2024.110816. Epub 2024 Aug 21.
CD4 T cells are an integral component of the adaptive immune response, carrying out many functions to combat a diverse range of pathogenic challenges. These cells exhibit remarkable plasticity, differentiating into specialized subsets such as T helper type 1 (T1), T2, T9, T17, T22, regulatory T cells (Tregs), and follicular T helper (T) cells. Each subset is capable of addressing a distinct immunological need ranging from pathogen eradication to regulation of immune homeostasis. As the immune response subsides, CD4 T cells rest down into long-lived memory phenotypes-including central memory (T), effector memory (T), resident memory (T), and terminally differentiated effector memory cells (T) that are localized to facilitate a swift and potent response upon antigen re-encounter. This capacity for long-term immunological memory and rapid reactivation upon secondary exposure highlights the role CD4 T cells play in sustaining both adaptive defense mechanisms and maintenance. Decades of mouse, human, and to a lesser extent, pig T cell research has provided the framework for understanding the role of CD4 T cells in immune responses, but these model systems do not always mimic each other. Although our understanding of pig immunology is not as extensive as mouse or human research, we have gained valuable insight by studying this model. More akin to pigs, our understanding of CD4 T cells in dogs is much less complete. This disparity exists in part because canine immunologists depend on paradigms from mouse and human studies to characterize CD4 T cells in dogs, with a fraction of available lineage-defining antibody markers. Despite this, every major CD4 T cell subset has been described to some extent in dogs. These subsets have been studied in various contexts, including in vitro stimulation, homeostatic conditions, and across a range of disease states. Canine CD4 T cells have been categorized according to lineage-defining characteristics, trafficking patterns, and what cytokines they produce upon stimulation. This review addresses our current understanding of canine CD4 T cells from a comparative perspective by highlighting both the similarities and differences from mouse, human, and pig CD4 T cell biology. We also discuss knowledge gaps in our current understanding of CD4 T cells in dogs that could provide direction for future studies in the field.
CD4 T细胞是适应性免疫反应的一个重要组成部分，执行多种功能以应对各种各样的致病挑战。这些细胞表现出显著的可塑性，可分化为特定的亚群，如1型辅助性T细胞（T1）、2型辅助性T细胞（T2）、9型辅助性T细胞（T9）、17型辅助性T细胞（T17）、22型辅助性T细胞（T22）、调节性T细胞（Tregs）和滤泡辅助性T细胞（Tfh）。每个亚群都能够满足从根除病原体到调节免疫稳态等不同的免疫需求。随着免疫反应消退，CD4 T细胞会静息为长寿记忆表型，包括中枢记忆T细胞（Tcm）、效应记忆T细胞（Tem）、组织驻留记忆T细胞（Trm）和终末分化效应记忆细胞（Temra），它们定位于特定部位以便在再次遇到抗原时迅速产生有力反应。这种长期免疫记忆和二次接触时快速重新激活的能力突出了CD4 T细胞在维持适应性防御机制和免疫平衡中所起的作用。数十年来对小鼠、人类以及在较小程度上对猪的T细胞研究为理解CD4 T细胞在免疫反应中的作用提供了框架，但这些模型系统并不总是相互模拟。虽然我们对猪免疫学的了解不如对小鼠或人类研究那样广泛，但通过研究这个模型我们已经获得了有价值的见解。与猪更相似的是，我们对犬类CD4 T细胞的了解要少得多。这种差异部分是因为犬类免疫学家依赖小鼠和人类研究的范式来表征犬类的CD4 T细胞，可用的谱系定义抗体标记物很少。尽管如此，在犬类中已经在一定程度上描述了每个主要的CD4 T细胞亚群。这些亚群已经在各种背景下进行了研究，包括体外刺激、稳态条件以及一系列疾病状态。犬类CD4 T细胞已根据谱系定义特征、迁移模式以及刺激时产生何种细胞因子进行了分类。本综述通过突出犬类与小鼠、人类和猪CD4 T细胞生物学的异同，从比较的角度阐述了我们目前对犬类CD4 T细胞的理解。我们还讨论了目前对犬类CD4 T细胞理解中的知识空白，这些空白可为该领域未来的研究提供方向。
