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

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(+)...

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Autores principales: Rabiger, Friederike V., Bismarck, Doris, Protschka, Martina, Köhler, Gabriele, Moore, Peter F., Büttner, Mathias, von Buttlar, Heiner, Alber, Gottfried, Eschke, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415905/
https://www.ncbi.nlm.nih.gov/pubmed/30865691
http://dx.doi.org/10.1371/journal.pone.0213597
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author Rabiger, Friederike V.
Bismarck, Doris
Protschka, Martina
Köhler, Gabriele
Moore, Peter F.
Büttner, Mathias
von Buttlar, Heiner
Alber, Gottfried
Eschke, Maria
author_facet Rabiger, Friederike V.
Bismarck, Doris
Protschka, Martina
Köhler, Gabriele
Moore, Peter F.
Büttner, Mathias
von Buttlar, Heiner
Alber, Gottfried
Eschke, Maria
author_sort Rabiger, Friederike V.
collection PubMed
description 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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spelling pubmed-64159052019-04-02 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 PLoS One Research Article 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. Public Library of Science 2019-03-13 /pmc/articles/PMC6415905/ /pubmed/30865691 http://dx.doi.org/10.1371/journal.pone.0213597 Text en © 2019 Rabiger et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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
title Canine tissue-associated CD4(+)CD8α(+) double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential
title_full Canine tissue-associated CD4(+)CD8α(+) double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential
title_fullStr Canine tissue-associated CD4(+)CD8α(+) double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential
title_full_unstemmed Canine tissue-associated CD4(+)CD8α(+) double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential
title_short Canine tissue-associated CD4(+)CD8α(+) double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential
title_sort canine tissue-associated cd4(+)cd8α(+) double-positive t cells are an activated t cell subpopulation with heterogeneous functional potential
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415905/
https://www.ncbi.nlm.nih.gov/pubmed/30865691
http://dx.doi.org/10.1371/journal.pone.0213597
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