Analysis of canine peripheral CD4+CD8+ double-positive T cell phenotype and function
Final Report Abstract
The field of comparative immunology, which aims to provide an in-depth understanding of the physiological and pathophysiological processes in different species, gains more and more importance. Considering high interspecies diversity of immune cells, it is essential to unveil species-specific characteristics. Dogs harbour a unique population of highly activated nonconventional TCRαβ+ CD4+CD8α+ double-positive (dp) T cells. In this project, we investigated the high immunological potential of dp T cells in peripheral blood of healthy dogs and identified distinct phenotypes and effector functions. Furthermore, the first systematic analysis of dp T cells in different organs revealed tissue-specific expression of effector and regulatory molecules as well as enrichment at mucosal sites such as the intestinal environment. These results form the basis for current investigations regarding the involvement of dp T cells in chronic enteropathy of the dog. As different non-conventional T cell populations may play important roles in immune homeostasis and inflammation, the research focus was expanded to enable comparison of dp T cells with other non-conventional TCRαβ and TCRγδ T cell populations of the dog. A surprisingly high frequency of non-conventional TCRαβ+ CD4−CD8α− double-negative (dn) T cells is present in peripheral blood and tissues under physiological conditions. Unique features of these TCRαβ+ dn T cells, compared with their less numerous human and murine counterparts, point to a role in immune regulation and in type 2 immunity such as anti-parasite responses and allergy. Albeit much lower in number, canine TCRγδ+ CD8α+ single-positive T cells and CD4-CD8α- dn T cells appear to express similar functional markers as those described in related veterinary species such as swine and chicken. Taken together, the data generated in this project not only contribute to a better understanding of T cell biology in dogs but also to comparative immunology.
Publications
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Canine peripheral blood CD4+CD8+ double-positive T cell subpopulations exhibit distinct T cell phenotypes and effector functions. Vet Immunol Immunopathol. 2017 Mar;185:48-56
Rothe K, Bismarck D, Büttner M, Alber G, von Buttlar H
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Canine tissue-associated CD4+CD8α+ double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential. PLoS One. 2019 Mar 13;14(3):e0213597
Rabiger FV, Bismarck D, Protschka M, Köhler G, Moore PF, Büttner M, von Buttlar H, Alber G, Eschke M
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Distinct Features of Canine Non-conventional CD4-CD8α- Double-Negative TCRαβ+ vs. TCRγδ+ T Cells. Front Immunol. 2019 Nov 22;10:2748
Rabiger FV, Rothe K, von Buttlar H, Bismarck D, Büttner M, Moore PF, Eschke M, Alber G
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2021. Tissue distribution and characteristics of canine nonconventional T cells. Doctoral thesis at University of Leipzig, Leipzig, Germany
Friederike V. Rabiger
