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

Research output: Contribution to journalArticle

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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T-cells
Canidae
T-lymphocytes
Tissue
T-Lymphocytes
dogs
Peyer's Patches
lymph nodes
Lymphocytes
Lymph Nodes
Peyer's patches
tissues
Chemical activation
lymphocytes
Dog Diseases
Computer peripheral equipment
Granzymes
Functional analysis
Flow cytometry
tissue analysis

ASJC Scopus subject areas

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

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Canine tissue-associated CD4 + CD8α + double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential . / Rabiger, Friederike V.; Bismarck, Doris; Protschka, Martina; Köhler, Gabriele; Moore, Peter F; Büttner, Mathias; Von Buttlar, Heiner; Alber, Gottfried; Eschke, Maria.

In: PloS one, Vol. 14, No. 3, e0213597, 01.03.2019.

Research output: Contribution to journalArticle

Rabiger, FV, Bismarck, D, Protschka, M, Köhler, G, Moore, PF, 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, vol. 14, no. 3, e0213597. https://doi.org/10.1371/journal.pone.0213597
Rabiger, Friederike V. ; Bismarck, Doris ; Protschka, Martina ; Köhler, Gabriele ; Moore, Peter F ; Büttner, Mathias ; Von Buttlar, Heiner ; Alber, Gottfried ; Eschke, Maria. / Canine tissue-associated CD4 + CD8α + double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential In: PloS one. 2019 ; Vol. 14, No. 3.
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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.",
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AU - Köhler, Gabriele

AU - Moore, Peter F

AU - Büttner, Mathias

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