Canine peripheral blood CD4 + CD8 +  double-positive T  cell subpopulations exhibit distinct T  cell phenotypes and effector functions

Rothe, Kathrin; Bismarck, Doris; Büttner, Mathias; Alber, Gottfried; Buttlar, Heiner von

doi:10.1016/j.vetimm.2017.01.005

Cited by 16 publications

(22 citation statements)

References 35 publications

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“…Accordingly, these cells lack expression of activation markers such as CD25 [30–32], which we could confirm in our study (Fig 4A and 4B). In contrast, mature CD4 + CD8α + dp T cells of secondary lymphatic and non-lymphatic tissues constitutively show high frequencies of CD25 expression (Fig 4A–4C), in line with our findings about CD4 + CD8α + dp T cells of the peripheral blood [14,15] and corresponding to an activated phenotype. Compared to their single-positive counterparts, frequencies of CD25 + T cells among CD4 + CD8α + dp T cells were significantly higher in all analyzed secondary lymphatic organs (tLN, mLN, spleen, PP).…”

Section: Resultssupporting

confidence: 91%

“…Canine CD4 + CD8α + double-positive (dp) T cells of peripheral blood are a heterogeneous effector memory T cell subpopulation suggesting an important role in immune response by their constitutively high activation [14,15]. Here we provide the first systematic characterization of CD4 + CD8α + dp T cells in different tissues within one homogeneous group of healthy Beagle dogs.…”

Section: Discussionmentioning

confidence: 99%

“…Canine CD4 + CD8α + dp T cells within peripheral blood mononuclear cells (PBMC) were first described around ten years ago [10–13]. To date, our group was able to characterize this unconventional T cell subpopulation in peripheral blood as mature T cell receptor (TCR) αβ + CD1a - effector memory T cells [14,15]. CD4 + CD8α + dp T cells can develop from both, CD4 + sp as well as from CD8α + sp T cells upon in vitro stimulation, but CD4 + sp T cells are the more potent progenitors [16].…”

Section: Introductionmentioning

confidence: 99%

“…CD4 dim CD8α bright , CD4 bright CD8α bright , and CD4 bright CD8α dim , which differ in phenotype and functional features. The CD4 dim CD8α bright subset expresses the CD8αβ heterodimer, whereas most cells of the other two subsets express the unconventional CD8αα homodimer [14,15]. In contrast to CD8αβ, CD8αα does not work as a TCR co-receptor, but was shown to negatively regulate the activation of T cells [17].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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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Section: Resultssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…As shown previously for dogs, the transcription factor T-bet is constitutively expressed by canine CD8α + sp, but only at a very low degree by CD4 + sp peripheral T cells (27). Similar to the latter, we observed significantly lower T-bet expression of both TCRαβ + and TCRγδ + CD4 − CD8α − dn T cells of canine PBMC in comparison to CD8α + sp T cells (Figure 6).…”

Section: Resultssupporting

confidence: 72%

Distinct Features of Canine Non-conventional CD4−CD8α− Double-Negative TCRαβ+ vs. TCRγδ+ T Cells

et al. 2019

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The role of conventional TCRαβ+CD4+ or TCRαβ+CD8α+ single-positive (sp) T lymphocytes in adaptive immunity is well-recognized. However, non-conventional T cells expressing TCRαβ or TCRγδ but lacking CD4 and CD8α expression [i.e., CD4−CD8α− double-negative (dn) T cells] are thought to play a role at the interface between the innate and adaptive immune system. Dn T cells are frequent in swine, cattle or sheep and predominantly express TCRγδ. In contrast, TCRγδ+ T cells are rare in dogs. In this study, we identified a high proportion of canine dn T cells in the TCRαβ+ T cell population of PBMC, lymphatic and non-lymphatic organs. In PBMC, the frequency of this T cell subpopulation made up one third of the frequency of TCRαβ+CD4+ sp, and almost half of the frequency of TCRαβ+CD8α+ sp T cells (i.e., ~15% of all TCRαβ+ T cells). Among TCRαβ+CD4−CD8α− dn T cells of PBMC and tissues, FoxP3+ cells were identified indicating regulatory potential of this T cell subset. 80% of peripheral blood FoxP3+TCRαβ+CD4−CD8α− dn T cells co-expressed CD25, and, interestingly, also the FoxP3-negative TCRαβ+CD4−CD8α− dn T cells comprised ~34% CD25+ cells. Some of the FoxP3-positive TCRαβ+CD4−CD8α− dn T cells co-expressed GATA-3 suggesting stable function of regulatory T cells. The frequency of GATA-3 expression by FoxP3−TCRαβ+CD4−CD8α− dn T cells was even higher as compared with TCRαβ+CD4+ sp T cells (20.6% vs. 11.9%). Albeit lacking FoxP3 and CD25 expression, TCRγδ+CD4−CD8α− dn T cells also expressed substantial proportions of GATA-3. In addition, TCRαβ+CD4−CD8α− dn T cells produced IFN-γ and IL-17A upon stimulation. T-bet and granzyme B were only weakly expressed by both dn T cell subsets. In conclusion, this study identifies two dn T cell subsets in the dog: (i) a large (~7.5% in Peyer's patches, ~15% in lung) population of TCRαβ+CD4−CD8α− dn T cells with subpopulations thereof showing an activated phenotype, high expression of FoxP3 or GATA-3 as well as production of IFN-γ or IL-17A and (ii) a small TCRγδ+CD4−CD8α− dn T cell subset also expressing GATA-3 without production of IFN-γ or IL-17A. It will be exciting to unravel the function of each subset during immune homeostasis and diseases of dogs.

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Flow Cytometry in Hematologic Neoplasia

Tarigo¹,

Seelig²,

Avery³

2022

Schalm's Veterinary Hematology

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Canine peripheral blood CD4 + CD8 + double-positive T cell subpopulations exhibit distinct T cell phenotypes and effector functions

Cited by 16 publications

References 35 publications

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

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

Distinct Features of Canine Non-conventional CD4−CD8α− Double-Negative TCRαβ+ vs. TCRγδ+ T Cells

Flow Cytometry in Hematologic Neoplasia

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