Rothe Kathrin, Bismarck Doris, Büttner Mathias, Alber Gottfried, von Buttlar Heiner
Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, 04103 Leipzig, Germany.
Vet Immunol Immunopathol. 2017 Mar;185:48-56. doi: 10.1016/j.vetimm.2017.01.005. Epub 2017 Jan 24.
Canine peripheral blood CD4CD8α double-positive (dp) Tcells represent a small population of T lymphocytes that are not only derived from single-positive (sp) CD4 but also from CD8 Tcells. Dp Tcells can be subdivided in three different subpopulations according to their expression levels of CD4 and CD8α, i.e. the CD4CD8α, CD4CD8α, and the CD4CD8α subsets. Previously we could show that total canine peripheral CD4CD8α dp Tcells have features of activated Tcells. Here we demonstrate that the individual dp Tcell subsets distinctly differ in their activation status and phenotype. Thus, among the dp Tcell subsets the CD4CD8α subpopulation has the lowest and the CD4CD8α subset the highest frequency of CD25 cells pointing to the CD4CD8α subset with the highest activation status. Consistent with that, analysis of CD44 vs. CD62L expression demonstrates that the CD4CD8α subset contains the highest frequencies of effector-memory Tcells (T). Upon in vitro stimulation, the CD4CD8α and CD4CD8α dp Tcell subsets show the highest frequencies of IFN-γ producing cells. Expression of granzyme B was found exclusively in the CD4CD8α dp Tcell subset indicating cytotoxic potential of this dp Tcell subset. Furthermore, T-bet expression was restricted to the CD4CD8α subset, while Foxp3 regulatory Tcells were detected in the CD4CD8α dp Tcell subset. In conclusion, canine dp Tcells are phenotypically and functionally heterogeneous consistent with the diverse characteristics of their single-positive CD4 and CD8 Tcell progenitors. The data provide the basis for future in vivo studies to elucidate the role of individual dp Tcell subsets in host defense and/or immune pathological diseases of dogs.
犬外周血CD4CD8α双阳性（dp）T细胞代表一小部分T淋巴细胞，它们不仅来源于单阳性（sp）CD4 T细胞，也来源于CD8 T细胞。根据CD4和CD8α的表达水平，dp T细胞可细分为三个不同的亚群，即CD4CD8α、CD4CD8α和CD4CD8α亚群。此前我们发现，犬外周血总CD4CD8α dp T细胞具有活化T细胞的特征。在此我们证明，各个dp T细胞亚群在活化状态和表型上存在明显差异。因此，在dp T细胞亚群中，CD4CD8α亚群的CD25细胞频率最低，而CD4CD8α亚群的频率最高，这表明CD4CD8α亚群的活化状态最高。与此一致，对CD44与CD62L表达的分析表明，CD4CD8α亚群中效应记忆T细胞（T）的频率最高。体外刺激后，CD4CD8α和CD4CD8α dp T细胞亚群产生IFN-γ的细胞频率最高。颗粒酶B仅在CD4CD8α dp T细胞亚群中表达，表明该dp T细胞亚群具有细胞毒性潜力。此外，T-bet表达仅限于CD4CD8α亚群，而在CD4CD8α dp T细胞亚群中检测到Foxp3调节性T细胞。总之，犬dp T细胞在表型和功能上具有异质性，与其单阳性CD4和CD8 T细胞祖细胞的不同特征一致。这些数据为未来体内研究阐明各个dp T细胞亚群在犬类宿主防御和/或免疫病理疾病中的作用提供了基础。
