Functional characterization of CD4+CD25+ regulatory T cells differentiated in vitro from bone marrow-derived haematopoietic cells of psoriasis patients with a family history of the disorder

2007 ◽  
Vol 158 (2) ◽  
pp. 298-305 ◽  
Author(s):  
K. Zhang ◽  
X. Li ◽  
G. Yin ◽  
Y. Liu ◽  
X. Niu ◽  
...  
2005 ◽  
Vol 65 (4) ◽  
pp. 1577-1586 ◽  
Author(s):  
Kui Shin Voo ◽  
Guangyong Peng ◽  
Zhong Guo ◽  
Tihui Fu ◽  
Yanchun Li ◽  
...  

2008 ◽  
Vol 69 (11) ◽  
pp. 745-750 ◽  
Author(s):  
Daniela Fenoglio ◽  
Francesca Ferrera ◽  
Marco Fravega ◽  
Piercesare Balestra ◽  
Florinda Battaglia ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2195-2195
Author(s):  
William J. Murphy ◽  
Isabel Bareo ◽  
Alan M. Hanash ◽  
Lisbeth A. Welniak ◽  
Kai Sun ◽  
...  

Abstract While a link between the innate to adaptive immune system has been established, studies demonstrating direct effects of T cells in regulating Natural Killer (NK) cell function have been lacking. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) have been shown to potently inhibit adaptive responses by T cells. We therefore investigated whether Tregs could affect NK cell function in vivo. Using a bone marrow transplantation (BMT) model of hybrid resistance, in which parental (H2d) marrow grafts are rejected by the NK cells of the F1 recipients (H2bxd), we demonstrate that the in vivo removal of host Tregs significantly enhances NK-cell mediated BM rejection. This heightened rejection was mediated by the specific NK cell Ly-49+ subset previously demonstrated to reject the BMC in this donor/host pairing. The depletion of Tregs could also further increase rejection already enhanced by treating recipients with the NK cell activator, poly I:C. Although splenic NK cell numbers were not significantly altered, increased splenic NK in vitro cytotoxic activity was observed from the recovered cells. The regulatory role of Tregs was confirmed in adoptive transfer studies in which transferred CD4+CD25+ Tregs resulted in abrogation of NK cell-mediated hybrid resistance. Thus, Tregs can potently inhibit NK cell function in vivo and their depletion may have therapeutic ramifications with NK cell function in BMT and cancer therapy.


2013 ◽  
Vol 9 (1) ◽  
pp. e1003140 ◽  
Author(s):  
Chun Li ◽  
Ilona Toth ◽  
Julian Schulze zur Wiesch ◽  
Florencia Pereyra ◽  
Jennifer Rychert ◽  
...  

2007 ◽  
Vol 13 (2) ◽  
pp. 191-199 ◽  
Author(s):  
Qi T. Yu ◽  
Masayuki Saruta ◽  
Armine Avanesyan ◽  
Phillip R. Fleshner ◽  
Alison H. Banham ◽  
...  

2019 ◽  
Vol 116 (8) ◽  
pp. 3106-3111 ◽  
Author(s):  
Young-Jun Park ◽  
Heeju Ryu ◽  
Garam Choi ◽  
Byung-Seok Kim ◽  
Eun Sook Hwang ◽  
...  

Expression of ectonucleotidase CD39 contributes to the suppressive activity of Foxp3+ regulatory T cells (Tregs) by hydrolyzing immunogenic ATP into AMP. The molecular mechanism that drives CD39 expression on Tregs remains elusive. We found that tumor-infiltrating Tregs (Ti-Tregs) failed to up-regulate CD39 in mice lacking EBI3 subunit of IL-27 or IL-27Ra. Mixed bone marrow chimera and in vitro studies showed that IL-27 signaling in Tregs directly drives CD39 expression on Ti-Tregs in a STAT1-dependent, but STAT3- and T-bet–independent, manner. Tregs stimulated with IL-27 showed enhanced suppressive activities against CD8+ T cell responses in vitro. Moreover, IL-27Ra–deficient Tregs and STAT1-deficient Tregs were less efficient than WT Tregs in suppressing antitumor immunity in vivo. CD39 inhibition significantly abolished IL-27–induced suppressive activities of Tregs. Thus, IL-27 signaling in Tregs critically contributes to protumorigenic properties of Tregs via up-regulation of CD39.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5605-5605
Author(s):  
Tzeon-Jye Chiou ◽  
Yi-Chun Ke ◽  
Chun-Tse Kuo ◽  
Hsiu-Yuan Huang ◽  
Shao-Chun Lu ◽  
...  

Background Foxp3+ regulatory T cells (Tregs) comprise of natural (n) and induced (i) Treg subsets play an important role in immune system. Currently, isolation of nTregs and in vitro-expanded nTregs was shown to be an effective therapy to GVHD patients. However, shortage of nTregs in peripheral blood and time consumption of expansion in vitro may eventually limit the clinical application. Conversely, iTregs can be generated in vitro from naïve T cells and to a large number of iTregs in short time. As we known, regulatory T cells would decay after a period of time, in vivo or in vitro. Keeping a certain number of iTregs during the GVHD treatment is necessary, it should be the best to provide iTregs to the patient more than single usage. Aim Manipulated supplements of TGF-β1-induced Foxp3+ regulatory T cells should be a good way for prevention from acute graft-versus-host disease within a short time. Investigation was performed via animal model. Methods Splenocytes from C57BL/6 mice were used as a source of naïve T cells by a CD4+ naïve T cell isolation Kit. To induce Foxp3+ regulatory T cells (iTregs), the CD4+ naïve T cells were incubated with anti-CD3/CD28 coated 24-well plate in the presence of IL-2 (20U/ml) and TGF-b1 (50ng/ml) for 3 days. Foxp3+iTregs were harvested and identified as the expressions of CD4+/CD25+/FoxP3+/CD127- via flow cytometry (Fig.1). In this experiment, recipients (BALB/c) were irradiated with 800cGy and then infused with donor (C57BL/6) bone marrow cells with (TCD-BM+CD4T) or without donor T cells (TCD-BM) by intravenous injection. TCD-BM+CD4T cells mice would appear aGVHD phenotype. 8x106 Foxp3+ iTregs were injected into the TCD-BM with donor T cell mouse one or twice (TCD-BM+CD4 T +iTreg) for immunosuppression assay as shown in Fig.2. Mouse GVHD phenotype, body weights and survival rates were investigated lasting for over 90 days. Tissue sections were stained with haematoxylin-eosin. Results According to our preliminary data, it indicated the injection of iTregs in the prevention of aGVHD should be feasible (Fig.3). Consequently, we have tried to investigate preventative efficiency of repeated iTregs supplements in TCD-BM mice. First of all, we compared the single-dose of iTregs with the repetition-dose of iTregs in aGVHD prevention. The data showed in Fig.4. The data showed that the survival rate was 73.3% in repeated treatment in mice, however, the survival rate was only 45.8% in single-dose of iTregs mice within 24 days. As the TCD-BM survival rate was 76.1%. It indicated that the repetition-dose of iTregs would prevent the occurrence of aGVHD, and the survival rate was similar as the bone marrow transplantation mice. The BM-CD4T mice with aGVHD phenotype could survive no more than 10 days. Furthermore, we investigated the survival time of the continual iTreg supplements mice. The data showed in Fig.5. After 90 days later, the body weight of iTregs treated mice could maintain the recovery efficiency to 83.8±2.1% and the survival rate to 78%, comparing with the TCD-BM mice was 88.8±0.6% and 73%. All of these mice could keep alive more than 90 days. Using histographic staining, we confirmed the aGVHD prevention with repeated supplement of Foxp3+iTregs to the CD4T mice (Fig.6). The mice, administration of CD4T cells with bone marrow cells, failed to survival for the serious damage of intestine villi (Fig.6A) and Peyer's patches (Fig.6B). In contrast, CD4T mice with Foxp3+-iTregs (iTregs) could survival more than 90 days and intestine villi were recovered after 90 days (Fig.6A). Peyer's patches are an important gut associated lymphoid tissue in small intestine and play a crucial role in immune response. Therefore, we have investigated the changes of Peyer's patches (Fig.6B). As the recovery of mice with iTregs for twice, the Peyer's patches reappeared after 90 days later. It indicated that keeping more iTregs in vivo could more efficient on prevention of aGVHD. It indicated that more alive iTregs to prevent GVHD occurrence more efficient and may provide the information pre-clinically. Conclusion We showed that repetition supplement of iTreg cells to TCD-BM+CD4T-treated mice, could maintain the mice in high survival rate. Therefore, we may provide more of the functional iTregs to GVHD patients, continuously. It's a good way to prevent the occurrence of GVHD. The result should develop a novel-cell based approach for potentially reducing the risk of acute GVHD clinically. Disclosures No relevant conflicts of interest to declare.


2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Geneve Awong ◽  
Rade Sajic ◽  
Ross La Motte‐Mohs ◽  
Alan Cochrane ◽  
Juan Carlos Zúñiga‐Pflücker

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