• Title, Summary, Keyword: Treg cells

Search Result 79, Processing Time 0.046 seconds

A Study of the Changes of T Helper 17 Cells and Regulatory T Cells in Herpes Zoster

  • Kim, Min Sung;Kim, Dong Jin;Na, Chan Ho;Shin, Bong Seok
    • Annals of dermatology
    • /
    • v.29 no.5
    • /
    • pp.578-585
    • /
    • 2017
  • Background: Immunosuppression and age-related deficiencies in cell-mediated immunity are important factors for the reactivation of latent varicella-zoster virus (VZV). $CD4^+CD25^+Foxp3^+$ regulatory T (Treg) cells and T helper 17 (Th17) cells are closely associated with various viral infections. Objective: We analyzed Treg cells and Th17 cells in patients with herpes zoster and investigated their relationship with the reactivation of latent VZV. Methods: Treg and Th17 cells in peripheral blood and the ratio of Th17 to Treg cells were examined in patients with herpes zoster and healthy controls. Changes between pre-treatment and post-treatment estimates of Treg and Th17 cells and clinical parameters in patients with herpes zoster were also analyzed. Results: The proportion of circulating Th17 cells and the Th17/Treg cell ratio were significantly higher in patients with herpes zoster than controls (p=0.012, 0.013), but there was no significant difference in the proportion of Treg cells between groups. There was no significant difference in the proportions of Treg and Th17 cells and the Th17/Treg cell ratio before and after treatment and between the non-postherpetic neuralgia and postherpetic neuralgia groups. Changes in Treg and Th17 cells and the Th17/Treg cell ratio were not significantly correlated with changes in the visual analog scale. Body surface area was significantly correlated with Treg cells, Th17 cells, and the Th17/Treg cell ratio (p=0.022, 0.002, 0.004). Conclusion: An imbalance between Th17 and Treg cells is associated with the reactivation of VZV, which may contribute to pathogenesis of herpes zoster.

Regulatory T Cell Therapy for Autoimmune Disease

  • Ha, Tai-You
    • IMMUNE NETWORK
    • /
    • v.8 no.4
    • /
    • pp.107-123
    • /
    • 2008
  • It has now been well documented in a variety of models that T regulatory T cells (Treg cells) play a pivotal role in the maintenance of self-tolerance, T cell homeostasis, tumor, allergy, autoimmunity, allograft transplantation and control of microbial infection. Recently, Treg cell are isolated and can be expanded in vitro and in vivo, and their role is the subject of intensive investigation, particularly on the possible Treg cell therapy for various immune-mediated diseases. A growing body of evidence has demonstrated that Treg cells can prevent or even cure a wide range of diseases, including tumor, allergic and autoimmune diseases, transplant rejection, graft-versus-host disease. Currently, a large body of data in the literature has been emerging and provided evidence that clear understanding of Treg cell work will present definite opportunities for successful Treg cell immunotherapy for the treatment of a broad spectrum of diseases. In this Review, I briefly discuss the biology of Treg cells, and summarize efforts to exploit Treg cell therapy for autoimmune diseases. This article also explores recent observations on pharmaceutical agents that abrogate or enhance the function of Treg cells for manipulation of Treg cells for therapeutic purpose.

Ribavirin Does Not Impair the Suppressive Activity of $Foxp3^+$ $ CD4^+$ $CD25^+$ Regulatory T Cells

  • Lee, Jeewon;Choi, Yoon Seok;Shin, Eui-Cheol
    • IMMUNE NETWORK
    • /
    • v.13 no.1
    • /
    • pp.25-29
    • /
    • 2013
  • Ribavirin is an antiviral drug used in combination with pegylated interferon-${\alpha}$ (IFN-${\alpha}$) for the treatment of hepatitis C virus (HCV) infection. Recently, ribavirin was reported to inhibit the suppressive activity of regulatory T (Treg) cells. In the present study, we re-evaluated the effect of ribavirin on $CD4^+$ $CD4^+$ $CD25^+$ Treg cells from normal donors. First, we examined the expression of CTLA-4 and CD39, which are known to play a role in the suppressive function of Treg cells. We found that ribavirin treatment did not modulate the expression of CTLA-4 and CD39 in Treg cells. We also studied the effect of ribavirin on Treg cells in the presence of IFN-${\alpha}$; however, the expression of CTLA-4 and CD39 in Treg cells was not changed by ribavirin in the presence of IFN-${\alpha}$. Next, we directly evaluated the effect of ribavirin on the suppressive activity of Treg cells in the standard Treg suppression assay, by co-culturing CFSE-labeled non-Treg $CD4^+$ T cells with purified Treg cells. We found that ribavirin did not attenuate the suppressive activity of Treg cells. Taken together, while ribavirin reversed Treg cell-mediated suppression of effector T cells in the previous study, we herein demonstrate that ribavirin does not impair the suppressive activity of Treg cells.

The Role of Regulatory T Cells in Cancer

  • Ha, Tai-You
    • IMMUNE NETWORK
    • /
    • v.9 no.6
    • /
    • pp.209-235
    • /
    • 2009
  • There has been an explosion of literature focusing on the role of regulatory T (Treg) cells in cancer immunity. It is becoming increasingly clear that Treg cells play an active and significant role in the progression of cancer, and have an important role in suppressing tumor-specific immunity. Thus, there is a clear rationale for developing clinical strategies to diminish their regulatory influences, with the ultimate goal of augmenting antitimor immunity. Therefore, manipulation of Treg cells represent new strategies for cancer treatment. In this Review, I will summarize and review the explosive recent studies demonstrating that Treg cells are increased in patients with malignancies and restoration of antitumor immunity in mice and humans by depletion or reduction of Treg cells. In addition, I will discuss both the prognostic value of Treg cells in tumor progression in tumor-bearing hosts and the rationale for strategies for therapeutic vaccination and immunotherapeutic targeting of Treg cells with drugs and microRNA.

Enforced Expression of CXCR5 Drives T Follicular Regulatory-Like Features in Foxp3+ T Cells

  • Kim, Young Uk;Kim, Byung-Seok;Lim, Hoyong;Wetsel, Rick A.;Chung, Yeonseok
    • Biomolecules & Therapeutics
    • /
    • v.25 no.2
    • /
    • pp.130-139
    • /
    • 2017
  • $CXCR5^+$ T follicular helper (Tfh) cells are associated with aberrant autoantibody production in patients with antibody-mediated autoimmune diseases including lupus. Follicular regulatory T (Tfr) cells expressing CXCR5 and Bcl6 have been recently identified as a specialized subset of $Foxp3^+$ regulatory T (Treg) cells that control germinal center reactions. In this study, we show that retroviral transduction of CXCR5 gene in $Foxp3^+$ Treg cells induced a stable expression of functional CXCR5 on their surface. The Cxcr5-transduced Treg cells maintained the expression of Treg cell signature genes and the suppressive activity. The expression of CXCR5 as well as Foxp3 in the transduced Treg cells appeared to be stable in vivo in an adoptive transfer experiment. Moreover, Cxcr5-transduced Treg cells preferentially migrated toward the CXCL13 gradient, leading to an effective suppression of antibody production from B cells stimulated with Tfh cells. Therefore, our results demonstrate that enforced expression of CXCR5 onto Treg cells efficiently induces Tfr cell-like properties, which might be a promising cellular therapeutic approach for the treatment of antibody-mediated autoimmune diseases.

Effects of Gastric Cancer Cells on the Differentiation of Treg Cells

  • Hu, Jing-Lan;Yang, Zhen;Tang, Jian-Rong;Fu, Xue-Qin;Yao, Lan-Jie
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.8
    • /
    • pp.4607-4610
    • /
    • 2013
  • The aim of this study was evaluated the prevalence of Treg cells in peripheral blood in patients with gastric cancer, and investigate the effect of gastric cancer cells on their differentiation. ELISA was employed to assess the concentrations of TGF-${\beta}$ and IL-10 in gastric cancer patients' serum. Then, mouse gastric cancer cells were co-cultured with T lymphocytes or T lymphocytes + anti-TGF-${\beta}$. Flow cytometric analysis and RT-PCR were then performed to detect Treg cells and TGF-${\beta}$ and IL-10 expression in gastric cancer cells. Our data showed that the expression of TGF-${\beta}$ and IL-10 in the patients with gastric cancer was increased compared to the case with healthy donors. The population of Treg cells and the expression levels of TGF-${\beta}$ and IL-10 in the co-culture group were much higher than in the control group (18.6% vs 9.5%) (P<0.05). Moreover, the population of Treg cells and the expression levels of TGF-${\beta}$ and IL-10 in the co-culture systerm were clearly decreased after addition of anti-TGF-${\beta}$ (7.7% vs 19.6%) (P<0.01). In conclusion, gastric cancer cells may induce Treg cell differentiation through TGF-${\beta}$, and further promote immunosuppression.

T Cell Receptor Signaling That Regulates the Development of Intrathymic Natural Regulatory T Cells

  • Song, Ki-Duk;Hwang, Su-Jin;Yun, Cheol-Heui
    • IMMUNE NETWORK
    • /
    • v.11 no.6
    • /
    • pp.336-341
    • /
    • 2011
  • T cell receptor (TCR) signaling plays a critical role in T cell development, survival and differentiation. In the thymus, quantitative and/or qualitative differences in TCR signaling determine the fate of developing thymocytes and lead to positive and negative selection. Recently, it has been suggested that self-reactive T cells, escape from negative selection, should be suppressed in the periphery by regulatory T cells (Tregs) expressing Foxp3 transcription factor. Foxp3 is a master factor that is critical for not only development and survival but also suppressive activity of Treg. However, signals that determine Treg fate are not completely understood. The availability of mutant mice which harbor mutations in TCR signaling mediators will certainly allow to delineate signaling events that control intrathymic (natural) Treg (nTreg) development. Thus, we summarize the recent progress on the role of TCR signaling cascade components in nTreg development from the studies with murine model.

Epirubicin Inhibits Soluble CD25 Secretion by Treg Cells Isolated from Diffuse Large B-cell Lymphoma Patients

  • Li, Lan-Fang;Wang, Hua-Qing;Liu, Xian-Ming;Ren, Xiu-Bao
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.3
    • /
    • pp.1721-1724
    • /
    • 2013
  • Objective: To investigate the effect of epirubicin on soluble CD25 (sCD25) secretion by CD4+CD25+ regulatory T (Treg) cells isolated from diffuse large B-cell lymphoma (DLBCL) patients. Methods: Treg cells were isolated from the peripheral blood mononuclear cells isolated from the newly diagnosed DBLCL patients. The concentration of sCD25 in the supernatant was determined with a commercial sCD25 (IL-2R) enzyme-linked immunosorbent assay (ELISA) kit. The fluorescence intensity of CD25 was detected by flow cytometry. Results: Cell survival rate was significantly decreased along with the increase of epirubicin concentration after treatment for 24 h. There was also a significant difference in the concentration of sCD25 between the epirubicin group and the control group (P<0.01). A positive correlation between the Treg cells survival rate and the concentration of sCD25 was detected (r=0.993, P<0.01). When equal numbers of CD4+CD25+ Treg cells of the epirubicin group and the control group were cultured for another 24 h without epirubicin the CD25 fluorescence intensity on the surface of Treg cells was obviously higher in the epirubicin group than that in the control group (P<0.01), while the sCD25 concentration in the supernatant in the epirubicin group was significantly lower than that in the control group (P<0.05). Conclusion: Epirubicin may improve the body's immune functions by inhibiting the sCD25 secretion by Treg cells in DLBCL patients.

Regulatory T Cells Promote Pancreatic Islet Function and Viability via TGF-β1 in vitro and in vivo (조절 T 세포 유래 TGF-β1에 의한 췌장섬세포의 기능 및 활성 증가)

  • Choi, Bongkum;Kim, Sa-Hyun
    • Korean Journal of Clinical Laboratory Science
    • /
    • v.50 no.3
    • /
    • pp.304-312
    • /
    • 2018
  • Regulatory T cells (Treg), known as immune-suppressors, may help modulate the immune response. In this study, we investigated the effect of Treg-derived $TGF-{\beta}1$ on pancreatic islet cell function in vitro and in vivo. One hundred eighty IEQ (islet equivalents) of pancreatic islets, the marginal amount to regulate blood glucose level after syngeneic islet transplantation in mouse type 1 diabetes (T1D) model, were co-cultured with $4{\times}10^6$ Treg cells for 48 hours. The changes in $TGF-{\beta}1$, interleukin-6 (IL-6), and insulin secretion levels were measured and analyzed among the Treg-only group, the islet-only group, and the Treg/islet co-cultured group. In the Treg/islet co-cultured group, IL-6 and insulin secretion levels were increased (P<0.0005, P<0.005) and islet viability was improved (P<0.005) compared with the islet-only group. Furthermore, after transplantation, the co-cultured islets regulated blood glucose levels efficiently in the T1D mouse model. These data suggest that Treg could improve islet functions and viability via the $TGF-{\beta}1$ secretion pathway (P<0.05~0.005), thus the use of Treg in islet transplantation should be explored further.

Associations Between Infiltrating Lymphocyte Subsets and Hepatocellular Carcinoma

  • Guo, Cun-Li;Yang, Hai-Chao;Yang, Xiu-Hua;Cheng, Wen;Dong, Tian-Xiu;Zhu, Wen-Jing;Xu, Zheng;Zhao, Liang
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.11
    • /
    • pp.5909-5913
    • /
    • 2012
  • Aims: We aimed to analyze the phenotype of tumor-infiltrating lymphocytes (TILs) and non-tumor infiltrating lymphocytes (NILs) in HCC and non-tumor tissues, and evaluate relationships between changes in these cells and the prognosis of HCC. Methods: Lymphocytes were isolated from HCC and corresponding non-tumor tissues and tested by flow cytometry. For comparison, clinical parameters were analyzed. Results: Compared with the non-tumor tissue, tumor tissue had a lower intensity of NK, NKT andCD8+T cell infiltration. TILs had higher intensity of CD4+CD25+Foxp3+regulatory T cell (Treg cells) infiltration compared with that in NILs. The prevalence of Treg cells was associated with fewer CD8 + T lymphocytes in the HCC immune microenvironment. The frequencies of NK cells and CD8+T cells in TILs of HCC patients with metastasis less than 12 months were lower than those without metastasis. However, the frequency of Treg cells was higher than those without metastasis. Conclusion: These results suggest that the frequencies of CD8+T, NK and NKT cells as well as Treg cells in the tumor tissue of HCC are significantly associated with patient survival, and could be applied as predictive indicators for HCC prognosis.