Regulatory T cells in dogs with multicentric lymphoma: peripheral blood quantification at diagnosis and after initial stage chemotherapy

Lymphoma is the most common hematopoietic malignancy in dogs and one of the most frequent among all neoplastic diseases in this species. It can occur in several anatomical locations with distinct histological and immunophenotypes. Depending on the host immune response towards the tumor, prognosis information could be collected. Because its well established immunosuppressant, antitumor activity, the function of regulatory T cells (Tregs) in canine neoplasias has been investigated. In this study, we sought to quantify, using flow cytometry, the Tregs subpopulation in peripheral blood of healthy dogs (10) and in those diagnosed with type-B (14) and type-T (8) multicentric lymphoma before (at diagnosis) and after the first cycle (5-week) of 19-week Madison-Wisconsin (MW) protocol of chemotherapy. Our results indicated that dogs with lymphoma showed higher percentage of Tregs (18,84±2,56) when compared to healthy dogs (4,70±0,50) (P<0,01). In addition, 5-week chemotherapy treatment reduced the Tregs subpopulation (7,54±1,08) to levels similar to control (4,70±0,50) (P>0,05). There was no difference in Tregs percentage between B-type (17,45±2,77) and T-type (21,27±5,27) lymphoma (P>0,05). With this, we conclude that canine lymphoma increases Tregs in the peripheral blood and the MW protocol of chemotherapy reduces this cell subpopulation to control values.

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Quantification of Treg cells in peripheral blood and lymph nodes of dogs with multicentric lymphoma

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/1678-4162-9599 ◽

2017 ◽

Vol 69 (6) ◽

pp. 1496-1502

Author(s):

L.A. Anai ◽

T.D. Munhoz ◽

L.M.S. Semolin ◽

N.P. Reis Filho ◽

E.M. Terra ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Immune Responses ◽

Lymph Nodes ◽

Peripheral Blood ◽

Treg Cells ◽

Control Group ◽

Significant Difference ◽

Healthy Dogs ◽

Multicentric Lymphoma

ABSTRACT Lymphoma is a malignant tumor characterized by cell proliferation of lymphoid origin and corresponds to 90% of all hematopoietic neoplasms of dogs. Regulatory T cells (Tregs) have been the target of many investigations in oncology due to their potential of down-regulating immune responses, as well as ensuring the maintenance of active mechanisms of tumor suppression. The aims of the present study were to compare the percentage of Tregs in peripheral blood between dogs with multicentric lymphoma and healthy animals, together with the percentage of Tregs in peripheral blood and lymph nodes of dogs with multicentric lymphoma. Twenty-six animals were enrolled in the study: 10 healthy dogs comprised the control group (CG) and 16 dogs with multicentric lymphoma comprised the Lymphoma Group (LG). We observed that dogs in the LG showed a significantly higher Tregs expression in peripheral blood compared to the CG. No significant difference was observed between Tregs expression in lymph nodes and peripheral blood of the LG, however. With these results, it is possible to conclude that multicentric lymphoma is a neoplasm with high Tregs expression, which poses this as a condition of interest when investigating treatments that can suppress Regulatory T cells.

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Quantitative analysis of CD4+CD25+FoxP3+ regulatory T-cells in canine atopic dermatitis in Korea

Veterinární Medicína ◽

10.17221/20/2019-vetmed ◽

2020 ◽

Vol 65 (No. 6) ◽

pp. 250-257

Author(s):

DJ Lee ◽

TH Chung ◽

C Park

Keyword(s):

T Cells ◽

Atopic Dermatitis ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Canine Atopic Dermatitis ◽

Healthy Dogs ◽

The Difference ◽

Circulating T Cells

Recently, it was suggested that CD4+CD25+FoxP3+ Tregs (Regulatory T-cells) exist in canine skin, although their numbers were not significantly different between healthy and atopic dogs. In this study, we investigated whether Treg frequencies correlate with the clinical features of canine atopic dermatitis (cAD). The goal of this study was to compare and analyse the numbers of the circulating Tregs in atopic and healthy dogs. In the peripheral blood mononuclear cells (PBMC) of healthy dogs, Tregs defined as CD4+CD25+FoxP3+ Tregs in the peripheral blood ranged from 0.3% to 1.5%. By contrast, in atopic dogs, the same population ranged from 0.7% to 8.8%. The percentage of CD4+CD25+FoxP3+ Tregs in gated CD4+ T-cells was significantly higher in the peripheral blood of dogs with atopic dermatitis (n = 9) than in the healthy controls (n = 8). The difference in the Treg levels (CD4+CD25+FoxP3+) (P = 0.012) between the atopic and the healthy groups was statistically significant. The circulating T-cells (phenotype CD4+CD25+FoxP3+ and CD4+FoxP3+) were increased significantly in the atopic dogs. The proportion of CD4+CD25+FoxP3+ Tregs of the atopic dogs decreased with advancing age. These findings suggest that changes in the Tregs may mediate the pathogenesis of CAD.

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Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽

10.3390/life11030245 ◽

2021 ◽

Vol 11 (3) ◽

pp. 245

Author(s):

Daniil Shevyrev ◽

Valeriy Tereshchenko ◽

Elena Blinova ◽

Nadezda Knauer ◽

Ekaterina Pashkina ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Autoimmune Diseases ◽

Peripheral Blood ◽

Treg Cells ◽

Homeostatic Proliferation ◽

Suppressive Activity ◽

Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

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Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis

Open Medicine ◽

10.1515/med-2021-0285 ◽

2021 ◽

Vol 16 (1) ◽

pp. 826-832

Author(s):

Jiarong Wang ◽

Liansheng Qiu ◽

Yimin Chen ◽

Minyun Chen

Keyword(s):

T Cells ◽

Allergic Rhinitis ◽

Retrospective Study ◽

Regulatory T Cells ◽

Visual Analog Scale ◽

Peripheral Blood ◽

Sublingual Immunotherapy ◽

Analog Scale ◽

Vas Score ◽

Medication Score

Abstract Background Few studies investigated the effects of sublingual immunotherapy (SLIT) on the peripheral regulatory T cells (Tregs)/Th17 ratio. Objective To investigate the effectiveness of SLIT in children with allergic rhinitis (AR) and the effects on the Tregs/Th17 ratio. Methods This was a retrospective study of children who were treated for AR between April 2017 and March 2018 at one hospital. The patients were grouped according to the treatments they received: SLIT + pharmacotherapy vs pharmacotherapy alone. Results Eighty children (51 boys and 29 girls; 40/group) were included. The visual analog scale (VAS) and medication scores at 1 year in the SLIT + pharmacotherapy group were 2.70 ± 1.08 and 1.1 ± 0.8, respectively, which were lower than at baseline (7.7 ± 1.2 and 3.6 ± 1.0, respectively) (both Ps < 0.05). For the pharmacotherapy group, the VAS score was decreased at 1 year vs baseline (3.3 ± 1.2 vs 7.4 ± 1.0; P < 0.05), but the medication score did not change (P > 0.05). In the SLIT + pharmacotherapy group, the Treg percentage increased, while the Th17 percentage decreased at 1 year (both Ps < 0.01). The percentages of Tregs and Th17s did not change in the pharmacotherapy group (both Ps > 0.05). Conclusions SLIT + pharmacotherapy can increase the Treg percentage and decrease the Th17 percentage in the peripheral blood of children with AR.

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