Open AccessCanine tissue-associated CD4+CD8α+ double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential
Author(s) -
Friederike V. Rabiger,
Doris Bismarck,
Martina Protschka,
Gabriele Köhler,
Peter F. Moore,
Mathias Büttner,
Heiner von Buttlar,
Gottfried Alber,
Maria Eschke
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0213597
Subject(s) - biology , cd8 , cytotoxic t cell , intraepithelial lymphocyte , lymphatic system , il 2 receptor , lymph node , t cell , population , microbiology and biotechnology , immunology , antigen , immune system , medicine , in vitro , biochemistry , environmental health
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.