Circulating CD4+CD25+ Regulatory T Cell and Th3 Cell of the Patients with Myelodysplastic Syndromes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4595-4595
Author(s):  
Zonghong Shao ◽  
Huaquan Wang ◽  
Limin Xing ◽  
Rong Fu ◽  
Fengmei Tu
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Mononuclear Cell ◽  
Cell Population ◽  
Myelodysplastic Syndromes ◽  
Regulatory T Cell ◽  
Peripheral Blood ◽  
Plasma Concentrations ◽  
Healthy Controls

Abstract Objective To investigate the quantitive and qualitive changes of peripheral blood CD4+CD25+ regulatory T cells and Th3 cells of the patients with myelodysplastic syndromes. Methods Whole peripheral blood samples of 40 MDS cases and 19 nromal control were assayed by flow cytometer for detecting the numbers of CD4+CD25+ regulatory T cell and CD3+CD4+TGFβ+ T cell(Th3). Expression of FOXP3 and TGF-β of peripheral blood mononuclear cell(PBMNC) were analysed by reverse transcriptase-polymerase chain reaction(RT-PCR). Commercial ELISA kits were used to measure plasma concentrations of TGF-β 1 according to the manufacturer’s instructions. Results. The percentage and number of CD4+CD25+ regulatory T cells in the CD4+T cell population were significantly higher in the peripheral blood of MDS patients than healthy controls[(21.5±2.2% vs 8.3±1.9%; P<0.05) and (76.1±20.6)×106/L vs (54.6±11.4)×106/L; P<0.05)]. The percentage and number of Th3 cells in the mononuclear cell population were significantly higher in the peripheral blood of MDS patients than healthy controls[(7.2±1.3%vs2.6±0.7%; P<0.01 and (63.5±15.2)×106/L vs (42.4±10.6)×106/L;P<0.05)]. The rate of expression of FOXP3 isolated from PBMNC was significantly higher in MDS patients than that in healthy controls (91.3% vs 52.6%; P<0.05%). But the expression of TGF-β of MDS patients didn’t significantly differ from that of healthy controls. The plasma level of TGF-β1 of MDS patients was significantly lower than that of healthy controls[(12.9±3.1)ng/ml vs (23.2±3.9)ng/ml; P<0.05)]. Conclusion The CD4+CD25 + regulatory T cells, Th3 cells and their inhibitive function increased in MDS, which might contribute to MDS clone escaping from immunosurveillance and gainning immunol privilege.

Increased Regulatory T Cell Subsets (TReg and Tr1 Cells) in the Peripheral Blood of Patients with Multiple Myeloma Correlate with Disease Stage.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5070-5070
Author(s):  
Sylvia Feyler ◽  
Lee Marles ◽  
Stevie Richards ◽  
Gordon Cook
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Population ◽  
Regulatory T Cell ◽  
Peripheral Blood ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Control Group ◽  
Refractory Disease

Abstract The immunologically hostile microenviroment of multiple Myeloma may contribute to the limited success of immunotherapy strategies. In addition to direct tumour-induced immunosuppression, tumour cells may generate suppressor cells to further suppress the immune effectors. Regulatory T-cells profoundly suppress immune responses and induce tolerance and 2 main subsets have been identified: Naturally Occurring TReg cells and Inducible regulatory Tr-1 cells. The association between tumour cells and regulatory T cells has not been studied in haematological malignancies, especially those of B lymphocyte lineages. Therefore, this the aim of this study is to determine if regulatory T-cell subsets are increased in the peripheral blood of patients with MM and how this varies with increasing disease burden. Peripheral blood from patients with MM (De novo, n=3; Low Disease burden, n=19; Relapsed/Refractory Disease, n=11) and MGUS (n=6) with a median age of 69 years old (range 39–89 yrs) were analysed by flow cytometry and compared to age-sex matched controls (n=20, median age 60 yrs, range 33–80 yrs). Whilst there was no significant difference in the absolute lymphocyte counts between MM patients and controls (1.58x109/l ±0.14 vs. 1.9x109/l ±0.1, p=0.05) a significant CD4+ T-cell lymphopenia was noted in patients with MM compared to controls (393±62 cells/μl vs. 849±95 cells/μl, p&lt;0.001). The CD4+ T-cell lymphopenia was most marked in patients with relapsed/refractory disease (462±114 cells/μl) and low tumour burden (380±85 cells/μl) compared with newly diagnosed patients (875±64 cells/μl, p&lt;0.001), MGUS (945±90 cells/μl, p&lt;0.001) and controls (849±95 cells/μl, p&lt;0.001). Using a sequential gating strategy, TReg cells were identified as CD4±/CD25+/GITR+ T-cells and expressed as a percentage of the CD4+T-cell population. Overall, patients with MM demonstrated a significant increase in the TReg cell population compared to the control group (15.0%±2.5 vs. 7.2%±1.1, p&lt;0.001). The increased TReg cell population was most marked in patients with relapsed/refractory disease (13.6%±1.5) and low tumour burden (16%±1.9) compared with newly diagnosed patients (6.7%±1.0, p&lt;0.001), MGUS (10.8%±1.7, p=0.03) and controls (7.2%±1.1, p&lt;0.001). Tr1 cells were analysed using an in-house assay and identified on a sequential gating strategy as CD4+/IL-10+/IL-4− T-cells and expressed as a percentage of the CD4+T-cell population. Overall, patients with MM demonstrated an increase in the Tr1 cell population compared to the control group (14.5%±5.5 vs. 9.8%±1.0) though the trend did not reach statistical significance (p=0.23). Similarly, an alteration in the Th1/Th2 balance was seen with an increase in the Th2 cell population compared to the control group (6.3%±3 vs. 2.8%±0.1) though the trend did not reach statistical significance (p=0.15). These results provide further evidence of immune dysregulation in patients with MM and suggest that tumour-associated immunosuppression may be mediated through the actions of regulatory T-cell subsets. In particular, the association with advanced disease stage suggests a casual association between the malignant cells and induction of immune regulatory cells. Further work in establishing a casual association between MM tumour cells and regulatory T-cells is on-going and is essential if immunotherapeutic strategies are ever to reach their full potential.

Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis

2021 ◽  
pp. 135245852110033
Author(s):  
Quentin Howlett-Prieto ◽  
Xuan Feng ◽  
John F Kramer ◽  
Kevin J Kramer ◽  
Timothy W Houston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
B Cell ◽  
Regulatory T Cell ◽  
Healthy Controls ◽  
Regulatory Cells ◽  
Long Term Treatment ◽  
Anti Cd20

Objective: To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients. Methods: 30 clinically stable MS patients, before and over 38 months of ocrelizumab treatment, were compared to 13 healthy controls, 29 therapy-naïve MS, 9 interferon-β-treated MS, 3 rituximab-treated MS, and 3 rituximab-treated patients with other autoimmune inflammatory diseases. CD8, CD28, CD4, and FOXP3 expression in peripheral blood mononuclear cells was quantitated with flow cytometry. Results: CD8+ CD28− regulatory cells rose from one-third of healthy control levels before ocrelizumab treatment (2.68% vs 7.98%), normalized by 12 months (13.5%), and rose to 2.4-fold above healthy controls after 18 months of ocrelizumab therapy (19.0%). CD4+ FOXP3+ regulatory cells were lower in MS than in healthy controls (7.98%) and showed slight long-term decreases with ocrelizumab. CD8+ CD28− and CD4+ FOXP3+ regulatory T cell percentages in IFN-β-treated MS patients were between those of untreated MS and healthy controls. Interpretation: Long-term treatment with ocrelizumab markedly enriches CD8+ CD28− regulatory T cells and corrects the low levels seen in MS before treatment, while slightly decreasing CD4+ FOXP3+ regulatory T cells. Homeostatic enrichment of regulatory CD8 T cells provides a mechanism, in addition to B cell depletion, for the benefits of anti-CD20 treatment in MS.

Human CD4+CD25+CD127− T Cells Show Potent Dose-Dependent Inhibition of Allogeneic DC-Driven MLRs.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5172-5172
Author(s):  
Rachel E. Protheroe ◽  
Colin G. Steward ◽  
Graziella Mazza ◽  
David C. Wraith
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Regulatory T Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Surface Expression ◽  
Widespread Application ◽  
Dose Dependent

Abstract Graft versus host disease (GVHD) is the primary cause of transplant related morbidity and mortality, limiting the widespread application of haemopoietic stem cell transplantation (HSCT). Evidence from murine models supports the role of CD4+CD25+ regulatory T cells in the suppression of GVHD. Human evidence regarding the role of regulatory T cells in alloresponses is conflicting and may reflect the difficulty in defining and isolating the regulatory T cell population in humans. We have investigated the use of peripheral blood monocyte-derived dendritic cells (DCs) as stimulator cells in allogeneic mixed lymphocyte reactions (MLRs), as a means of assessing the in vitro suppressive function of regulatory T cells in human alloresponses. Peripheral blood mononuclear cells (PBMCs) were obtained from healthy adult volunteers. Magnetically isolated CD4+CD25+ T cells were combined with 50×103 autologous PBMCs or 20×103 autologous CD4+ T cells as responders, and 5×103 allogeneic irradiated DCs. Proliferation was assessed by tritiated thymidine incorporation. The CD4+CD25+ cells were anergic and demonstrated dose-dependent suppression of responder cell proliferation in the DC-driven allogeneic MLR. Greater than 50% suppression was seen with CD4+CD25+ T cells co-cultured with responder PBMCs at ratios of 1:4 to 1:32. Furthermore, depletion of CD4+CD25+ T cells from whole CD4+ responder cells resulted in enhanced proliferation and an increase in the amplitude of the MLR. Flow cytometry indicated that the majority of the magnetically isolated CD4+CD25+ T cells were FoxP3+ on intracellular staining and demonstrated down-regulation of cell surface expression of the IL-7 receptor (CD127). The potent suppression demonstrated here by CD4+CD25+CD127− T cells at ratios of 1:32 responder cells, suggests that these cells have a potential role for suppressing alloresponses at physiological levels. Moreover, this assay provides the basis for future investigation into regulatory T cell function in patients post-HSCT.

scholarly journals Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽  
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.

scholarly journals Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood

Rheumatology ◽  
2006 ◽  
Vol 45 (10) ◽  
pp. 1210-1217 ◽  
Author(s):  
C. A. Lawson ◽  
A. K. Brown ◽  
V. Bejarano ◽  
S. H. Douglas ◽  
C. H. Burgoyne ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Cell Population ◽  
Early Rheumatoid Arthritis ◽  
Regulatory T Cell ◽  
Peripheral Blood

scholarly journals Regulatory T Cells Contribute to Resistance against Lyme Arthritis

2020 ◽  
Vol 88 (11) ◽  
Author(s):  
Emily M. Siebers ◽  
Elizabeth S. Liedhegner ◽  
Michael W. Lawlor ◽  
Ronald F. Schell ◽  
Dean T. Nardelli
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lyme Disease ◽  
Regulatory T Cells ◽  
Regulatory T Cell ◽  
Interleukin 10 ◽  
Lyme Arthritis ◽  
Interleukin 17 ◽  
Content Type

ABSTRACT The symptoms of Lyme disease are caused by inflammation induced by species of the Borrelia burgdorferi sensu lato complex. The various presentations of Lyme disease in the population suggest that differences exist in the intensity and regulation of the host response to the spirochete. Previous work has described correlations between the presence of regulatory T cells and recovery from Lyme arthritis. However, the effects of Foxp3-expressing CD4+ T cells existing prior to, and during, B. burgdorferi infection have not been well characterized. Here, we used C57BL/6 “depletion of regulatory T cell” mice to assess the effects these cells have on the arthritis-resistant phenotype characteristic of this mouse strain. We showed that depletion of regulatory T cells prior to infection with B. burgdorferi resulted in sustained swelling, as well as histopathological changes, of the tibiotarsal joints that were not observed in infected control mice. Additionally, in vitro stimulation of splenocytes from these regulatory T cell-depleted mice resulted in increases in gamma interferon and interleukin-17 production and decreases in interleukin-10 production that were not evident among splenocytes of infected mice in which Treg cells were not depleted. Depletion of regulatory T cells at various times after infection also induced rapid joint swelling. Collectively, these findings provide evidence that regulatory T cells existing at the time of, and possibly after, B. burgdorferi infection may play an important role in limiting the development of arthritis.

scholarly journals Thymic Regulatory T Cell Development: Role of Signalling Pathways and Transcription Factors

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Mark Engel ◽  
Tom Sidwell ◽  
Ajithkumar Vasanthakumar ◽  
George Grigoriadis ◽  
Ashish Banerjee
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Tolerance ◽  
Regulatory T Cell ◽  
T Cell Development ◽  
Signalling Pathways ◽  
Treg Development

Regulatory T cells (Tregs) are a subset of CD4 T cells that are key mediators of immune tolerance. Most Tregs develop in the thymus. In this review we summarise recent findings on the role of diverse signalling pathways and downstream transcription factors in thymic Treg development.

scholarly journals The Transcriptional Differences of Avian CD4+CD8+ Double-Positive T Cells and CD8+ T Cells From Peripheral Blood of ALV-J Infected Chickens Revealed by Smart-Seq2

2021 ◽  
Vol 11 ◽  
Author(s):  
Manman Dai ◽  
Li Zhao ◽  
Ziwei Li ◽  
Xiaobo Li ◽  
Bowen You ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Signaling Pathway ◽  
Cell Population ◽  
Peripheral Blood ◽  
T Cell Response ◽  
T Cell Subsets ◽  
High Expression ◽  
Receptor Interaction ◽  
Double Positive

It is well known that chicken CD8+ T cell response is vital to clearing viral infections. However, the differences between T cell subsets expressing CD8 receptors in chicken peripheral blood mononuclear cells (PBMCs) have not been compared. Herein, we used Smart-Seq2 scRNA-seq technology to characterize the difference of chicken CD8high+, CD8high αα+, CD8high αβ+, CD8medium+, and CD4+CD8low+ T cell subsets from PBMCs of avian leukosis virus subgroup J (ALV-J)-infected chickens. Weighted gene co-expression network analysis (WGCNA) and Trend analysis revealed that genes enriched in the “Cytokine–cytokine receptor interaction” pathway were most highly expressed in the CD8high αα+ T cell population, especially T cell activation or response-related genes including CD40LG, IL2RA, IL2RB, IL17A, IL1R1, TNFRSF25, and TNFRSF11, suggesting that CD8high αα+ T cells rather than other CD8 subpopulations were more responsive to ALV-J infections. On the other hand, genes involved in the “FoxO signaling pathway” and “TGF-beta signaling pathway” were most highly expressed in the CD4+CD8low+ (CD8low+) T cell population and the function of CD4+CD8low+ T cells may play roles in negatively regulating the functions of T cells based on the high expression of CCND1, ROCK1, FOXO1, FOXO3, TNFRSF18, and TNFRSF21. The selected gene expressions in CD8+ T cells and CD4+CD8low+ double-positive T cells confirmed by qRT-PCR matched the Smart-Seq2 data, indicating the reliability of the smart-seq results. The high expressions of Granzyme K, Granzyme A, and CCL5 indicated the positive response of CD8+ T cells. Conversely, CD4+CD8+ T cells may have the suppressor activity based on the low expression of activation molecules but high expression of T cell activity suppressor genes. These findings verified the heterogeneity and transcriptional differences of T cells expressing CD8 receptors in chicken PBMCs.

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