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犬类健康与疾病中的记忆 T 细胞亚群。

Canine memory T-cell subsets in health and disease.

机构信息

Louisiana State University, School of Veterinary Medicine, Department of Veterinary Clinical Sciences, Skip Bertman Dr., Baton Rouge, LA, 70806, USA.

Louisiana State University, School of Veterinary Medicine, Department of Veterinary Clinical Sciences, Skip Bertman Dr., Baton Rouge, LA, 70806, USA.

出版信息

Vet Immunol Immunopathol. 2022 Apr;246:110401. doi: 10.1016/j.vetimm.2022.110401. Epub 2022 Feb 12.

Abstract

A more complete understanding of canine T-lymphocyte immunity is necessary for improving diagnostic and therapeutic approaches to canine diseases, developing cell-based canine immunotherapeutics, and evaluating dogs as large mammal models for comparative immunology research. The aim of this study was to utilize CD45RA (indicating antigen inexperience) and CD62L (indicating lymph node homing capability), to quantify canine memory T-cell subsets in healthy dogs and dogs with various diseases. Peripheral blood mononuclear cells (PBMCs) were prospectively collected from dogs belonging to one of four groups:dermatologic inflammation (n = 9), solid tumors (n = 9), lymphoma (n = 9), and age-/weight-matched healthy control dogs (n = 15). Dogs receiving prednisone or any other immunomodulating medication within two weeks were excluded. Flow cytometry was performed and T-cell subsets were defined as CD4+ or CD8+, and naïve (TN), central memory (CM), effector memory (EM), or terminal effector memory re-expressing CD45RA (TEMRA). T-cell subset proportions were compared between each disease group and their healthy age-/weight-matched controls using a Mann-Whitney test. Significantly increased %CD8+ TN (P = 0.036) and decreased %CD8+ TEMRA (P = 0.045) were detected in dogs with dermatologic inflammation compared to healthy controls. Furthermore, %CD4+ TN positively correlated with Canine Atopic Dermatitis Extent and Severity Index (CADESI) score within the inflammation group (ρ = 0.817, P = 0.011). No significant differences between either cancer group and their healthy controls were detected. Taken together, these data indicate that dermatologic inflammation can alter proportions of peripheral blood T-cell subsets, possibly due to the migration of antigen-specific T-cells into tissues. Furthermore, these findings support the utility of CD45RA and CD62L in characterizing clinical canine immune responses.

摘要

为了改善犬病的诊断和治疗方法、开发基于细胞的犬免疫疗法以及评估犬作为大型哺乳动物比较免疫学研究的模型,我们需要更全面地了解犬的 T 淋巴细胞免疫。本研究旨在利用 CD45RA(表示抗原无经验)和 CD62L(表示淋巴结归巢能力),定量检测健康犬和患有各种疾病犬的记忆性 T 细胞亚群。前瞻性地收集属于以下四个组之一的犬外周血单核细胞(PBMC):皮肤炎症(n=9)、实体瘤(n=9)、淋巴瘤(n=9)和年龄/体重匹配的健康对照组犬(n=15)。两周内接受泼尼松或任何其他免疫调节药物治疗的犬被排除在外。进行流式细胞术,将 T 细胞亚群定义为 CD4+或 CD8+,并将其分为初始(TN)、中央记忆(CM)、效应记忆(EM)或重新表达 CD45RA 的终末效应记忆(TEMRA)。使用曼-惠特尼检验比较每个疾病组与其健康年龄/体重匹配对照组之间的 T 细胞亚群比例。与健康对照组相比,皮肤炎症组犬的 CD8+TN(%)(P=0.036)显著增加,而 CD8+TEMRA(%)(P=0.045)显著减少。此外,在炎症组内,CD4+TN 与犬特应性皮炎严重程度指数(CADESI)评分呈正相关(ρ=0.817,P=0.011)。未发现癌症组与健康对照组之间存在显著差异。总之,这些数据表明,皮肤炎症可能会改变外周血 T 细胞亚群的比例,这可能是由于抗原特异性 T 细胞向组织迁移所致。此外,这些发现支持 CD45RA 和 CD62L 用于描述临床犬免疫反应的效用。

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