Canine tissue-associated CD4 + CD8α + double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential

Friederike V. Rabiger, Doris Bismarck, Martina Protschka, Gabriele Köhler, Peter F Moore, Mathias Büttner, Heiner Von Buttlar, Gottfried Alber, Maria Eschke

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Abstract

Canine CD4 + CD8α + double-positive (dp) T cells of peripheral blood are a unique effector memory T cell subpopulation characterized by an increased expression of activation markers in comparison with conventional CD4 + or CD8α + single-positive (sp) T cells. In this study, we investigated CD4 + CD8α + dp T cells in secondary lymphatic organs (i.e. mesenteric and tracheobronchial lymph nodes, spleen, Peyer’s patches) and non-lymphatic tissues (i.e. lung and epithelium of the small intestine) within a homogeneous group of healthy Beagle dogs by multi-color flow cytometry. The aim of this systematic analysis was to identify the tissue-specific localization and characteristics of this distinct T cell subpopulation. Our results revealed a mature extrathymic CD1a - CD4 + CD8α + dp T cell population in all analyzed organs, with highest frequencies within Peyer’s patches. Constitutive expression of the activation marker CD25 is a feature of many CD4 + CD8α + dp T cells independent of their localization and points to an effector phenotype. A proportion of lymph node CD4 + CD8α + dp T cells is FoxP3 + indicating regulatory potential. Within the intestinal environment, the cytotoxic marker granzyme B is expressed by CD4 + CD8α + dp intraepithelial lymphocytes. In addition, a fraction of CD4 + CD8α + dp intraepithelial lymphocytes and of mesenteric lymph node CD4 + CD8α + dp T cells is TCRγδ + . However, the main T cell receptor of all tissue-associated CD4 + CD8α + dp T cells could be identified as TCRαβ. Interestingly, the majority of the CD4 + CD8α + dp T cell subpopulation expresses the unconventional CD8αα homodimer, in contrast to CD8α + sp T cells, and CD4 + CD8α + dp thymocytes which are mainly CD8αβ + . The presented data provide the basis for a functional analysis of tissue-specific CD4 + CD8α + dp T cells to elucidate their role in health and disease of dogs.

Original languageEnglish (US)
Article numbere0213597
JournalPloS one
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2019

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Rabiger, F. V., Bismarck, D., Protschka, M., Köhler, G., Moore, P. F., Büttner, M., Von Buttlar, H., Alber, G., & Eschke, M. (2019). Canine tissue-associated CD4 + CD8α + double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential PloS one, 14(3), [e0213597]. https://doi.org/10.1371/journal.pone.0213597