Canine CD4+CD8+ double-positive T cells can develop from CD4+ and CD8+ T cells

Bismarck, Doris; Moore, Peter F.; Alber, Gottfried; Buttlar, Heiner von

doi:10.1016/j.vetimm.2014.09.008

Cited by 10 publications

(8 citation statements)

References 24 publications

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“…The low number of SP cells observed in the infected dogs of our study may be due to acquisition of the DP phenotype outside of the thymus or due to the liberation of immature cells into the bloodstream. The CD4+ and CD8+ cells can act as progenitors of DP cells, as described previously in dogs (Bismarck et al, 2014), as well as in swine (Saalmuller et al, 2002) and humans (Blue et al, 1986;Nascimbeni et al, 2004;Parel and Chizzolini, 2004;Schenkel et al, 2010). The extrathymic origin of DP T cells was reported in several others species, such as mice, rats, chickens, monkeys, swine and humans, and there appears to be no predilection of localisation, as reviewed by Overgaard et al (2015).…”

Section: Discussionmentioning

confidence: 57%

T lymphocyte immunophenotypes in the cerebrospinal fluid of dogs with visceral leishmaniasis

Grano

Silva

Melo

et al. 2016

Veterinary Parasitology

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Visceral leishmaniasis (VL) is a disease causing several clinical manifestations in dogs, including neurological disorders. Nevertheless, there are few studies related to the evaluation of the brain alterations during VL. Evidences of the involvement of cerebral barriers in infected dogs was reported, including the presence of brain inflammatory infiltrate, with a predominance of CD3+ T cells. Therefore, the aim of this study was to determine the immunophenotypes of T lymphocytes in the cerebrospinal fluid (CSF), as well as in peripheral blood, and to correlate with brain alterations in dogs with VL. We detected elevated percentages of double negative (DN) and double positive (DP) T cells in the CSF, with a predominance of TCRαb. In the histopathological analysis, we observed a predominance of lymphoplasmacytic infiltrate, mainly in leptomeninges, ranging from mild to intense, and we observed a positive correlation between the intensity of inflammation in the subependymal area and the DN T cells of the CSF. Thus, the DN T cells seem be acting as villains of the immune system through pro-inflammatory mechanisms. Further, the proportion of the different population of CSF T cells did not differ from those observed in the blood, which provides us with more evidence of blood-CSF barrier breakdown. Together, the results provide more explanation to the inflammation observed in the brain of dogs with VL, which the DN T cells contribute to the origin and progression of the neurological disease. This study provides insight into the immunophenotypes of T lymphocytes in the CSF during canine visceral leishmaniasis.

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Section: Discussionmentioning

confidence: 57%

T lymphocyte immunophenotypes in the cerebrospinal fluid of dogs with visceral leishmaniasis

Grano

Silva

Melo

et al. 2016

Veterinary Parasitology

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“…Interestingly, TcES also caused increased Foxp3 expression in CD4+ CD8+ double-positive T cells. In dogs, this subset represents a heterogeneous population of activated T cells in the peripheral blood that can develop from CD4+ and CD8+ T cells 47 . Our observation that these cells express Foxp3 is in accordance to a previous study on canine Tregs in the peripheral blood and popliteal lymph node 48 .…”

Section: Discussionmentioning

confidence: 99%

Zoonotic intestinal helminths interact with the canine immune system by modulating T cell responses and preventing dendritic cell maturation

Junginger

Raue

Wolf

et al. 2017

Sci Rep

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Parasite co-evolution alongside the mammalian immune system gave rise to several modulatory strategies by which they prevent exaggerated pathology and facilitate a longer worm survival. As little is known about the immunoregulatory potential of the zoonotic canine parasites Ancylostoma caninum and Toxocara canis in the natural host, the present study aimed to investigate whether their larval excretory-secretory (ES) products can modulate the canine immune system. We demonstrated TcES to increase the frequency of CD4+ Foxp3high T cells, while both AcES and TcES were associated with elevated Helios expression in Foxp3high lymphocytes. ES products were further capable of inducing IL-10 production by lymphocytes, which was mainly attributed to CD8+ T cells. ES treatment of PBMCs prior to mitogen stimulation inhibited polyclonal proliferation of CD4+ and CD8+ T cells. Moreover, monocyte-derived ES-pulsed dendritic cells reduced upregulation of MHC-II and CD80 in response to lipopolysaccharide. The data showed that regulation of the canine immune system by A. caninum and T. canis larvae comprises the modification of antigen-specific and polyclonal T cell responses and dendritic cell maturation.

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“…This alternative hypothesis suggests that mature, peripheral, SP T cells up-regulate either the CD4 or the CD8 coreceptor [2]. In support of this theory, canine DP T cells at peripheral sites can originate from both CD4 + and CD8 + SP T cells upon in vitro stimulation [11,12]. Moreover, the expression of memory T cell markers by peripheral DP T cells casts further doubt on these cells being premature extrathymic DP thymocytes [13][14][15][16].…”

Section: Introductionmentioning

confidence: 98%

CD4+CD8β+ double-positive T cells in skin-draining lymph nodes respond to inflammatory signals from the skin

Overgaard

Cruz

Bridge

et al. 2017

Journal of Leukocyte Biology

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CD4CD8 double-positive (DP), mature, peripheral T cells are readily detectable in a variety of species and tissues. Despite a common association with autoimmune and malignant skin disorders, however, little is understood about their role or function. Herein, we show that DP T cells are readily detectable in the blood, spleen, and peripheral lymph nodes of naïve C57BL/6 mice. DP T cells were also present in Jα18 and CD1d mice, indicating that these cells are not NK-T cells. After skin administration of CASAC adjuvant, but not Quil A adjuvant, both total DP T cells and skin-infiltrating DP T cells increased in number. We explored the possibility that DP T cells could represent aggregates between CD4 and CD8 single-positive T cells and found strong evidence that a large proportion of apparent DP T cells were indeed aggregates. However, the existence of true CD4CD8 DP T cells was confirmed by Amnis ImageStream (Millipore Sigma, Billerica, MA, USA) imaging. Multiple rounds of FACS sorting separated true DP cells from aggregates and indicated that conventional analyses may lead to ∼10-fold overestimation of DP T cell numbers. The high degree of aggregate contamination and overestimation of DP abundance using conventional analysis techniques may explain discrepancies reported in the literature for DP T cell origin, phenotype, and function.

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Canine CD4+CD8+ double-positive T cells can develop from CD4+ and CD8+ T cells

Cited by 10 publications

References 24 publications

T lymphocyte immunophenotypes in the cerebrospinal fluid of dogs with visceral leishmaniasis

T lymphocyte immunophenotypes in the cerebrospinal fluid of dogs with visceral leishmaniasis

Zoonotic intestinal helminths interact with the canine immune system by modulating T cell responses and preventing dendritic cell maturation

CD4+CD8β+ double-positive T cells in skin-draining lymph nodes respond to inflammatory signals from the skin

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