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Treg methotrexate

O Rofe, G Bar-Sela, Z Keidar, T Sezin, C D Sadik, R Bergman
Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T-cells and T-regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death-1 (PD-1) : programmed death ligand (PD-L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti-PD-1) therapy following unsuccessful treatment with ipilimumab [anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4]...
April 2017: Clinical and Experimental Dermatology
Matthias Klein, Marc Schmalzing, Giovanni Almanzar, Sandrine Benoit, Henning Hamm, Hans-Peter Tony, Matthias Goebeler, Martina Prelog
Only limited attention has been paid to the role of CD8 + T cells in the etiopathogenesis and progression of systemic sclerosis (SSc). CD8 + T cells may have autoantigen-specific and pro-inflammatory but also immunomodulatory properties. To investigate the differentiation of CD8 + T cells, staining of cell surface factors and of chemokine receptors were performed. In addition, the cytokine-producing ability of circulating CD8 + T cells and their sensitivity to suppression by regulatory T cells (Tregs) were compared between patients with diffuse (dcSSc) or limited cutaneous SSc (lcSSc) and healthy individuals...
August 25, 2016: Autoimmunity
Francis Bonnefoy, Anna Daoui, Séverine Valmary-Degano, Eric Toussirot, Philippe Saas, Sylvain Perruche
BACKGROUND: Apoptotic cell-based therapies have been proposed to treat chronic inflammatory diseases. The aim of this study was to investigate the effect of intravenous (i.v.) apoptotic cell infusion in ongoing collagen-induced arthritis (CIA) and the interaction of this therapy with other treatments used in rheumatoid arthritis (RA), including methotrexate (MTX) or anti-TNF therapy. METHODS: The effects of i.v. apoptotic cell infusion were evaluated in a CIA mouse model in DBA/1 mice immunized with bovine type II collagen...
2016: Arthritis Research & Therapy
Songsong Li, Zhenzhou Wu, Ling Li, Xuehua Liu
BACKGROUND The aim of this study was to investigate the protective effect of interleukin-6 (IL-6) receptor antagonist tocilizumab (TCZ) on rheumatoid arthritis (RA) and its related mechanism. MATERIAL AND METHODS Thirty RA patients receiving long-term methotrexate therapy at moderate and severe active stages were selected and treated with TCZ 8 mg/kg/time iv gtt intravenously guttae every 4 weeks. Peripheral blood was extracted before and 24 weeks after TCZ treatment. Peripheral blood mononuclear cells (PBMC) were collected by density gradient centrifugation...
June 20, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Norailys Lorenzo, Fiorella Altruda, Lorenzo Silengo, Maria Del Carmen Dominguez
Induction of tolerance to autoantigens in vivo is a complex process that involves several mechanisms such as the induction of regulatory T cells and changes in the cytokine and chemokine profiles. This approach represents an attractive alternative for treatment of autoimmune diseases. APL-1 is an altered peptide ligand derived from a novel CD4 + T cell epitope of human heat-shock protein of 60 kDa (HSP60), an autoantigen involved in the pathogenesis of rheumatoid arthritis (RA). We have shown previously that this peptide efficiently inhibited the course of adjuvant-induced arthritis in Lewis rats and induced regulatory T cell (Treg) in ex vivo assay with PBMC isolated from RA patients...
May 2017: Clinical and Experimental Medicine
Yaxiong Deng, Christopher Chang, Qianjin Lu
Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of psoriasis is complex and the exact mechanism remains elusive. However, psoriasis is thought to result from a combination of genetic, epigenetic, and environmental influences. Recent studies have identified that epigenetic factors including dysregulated DNA methylation levels, abnormal histone modification and microRNAs expressions are involved in the development of psoriasis...
June 2016: Clinical Reviews in Allergy & Immunology
Fabrício Figueiró, Catiúscia P de Oliveira, Letícia S Bergamin, Liliana Rockenbach, Franciane B Mendes, Elisa Helena F Jandrey, Cesar Eduardo J Moritz, Letícia F Pettenuzzo, Jean Sévigny, Silvia S Guterres, Adriana R Pohlmann, Ana Maria O Battastini
Glioblastoma multiforme (GBM) is a deadly cancer characterized by a pro-tumoral immune response. T-regulatory (Treg) lymphocytes suppress effector immune cells through cytokine secretion and the adenosinergic system. Ecto-5'-nucleotidase/CD73 plays a crucial role in Treg-mediated immunosuppression in the GBM microenvironment (GME). Methotrexate (MTX) is an immunosuppressive drug that can increase the extracellular concentration of adenosine. In this manuscript, C6 GBM cells were treated with 1.0 μM MTX, and ecto-5'-nucleotidase/CD73 expression and extracellular AMP metabolism were analyzed in vitro...
June 2016: Purinergic Signalling
Nicolas Andre, Sylvie Cointe, Vincent Barlogis, Laurent Arnaud, Romaric Lacroix, Eddy Pasquier, Françoise Dignat-George, Gérard Michel, Florence Sabatier
Maintenance chemotherapy is an important part of the treatment of ALL in children. It relies on the long-term oral administration of daily low-dose mercaptopurin and weekly low-dose methotrexate. Although it has been used in the clinic for decades, its mechanisms of action remain unclear. Here, we investigated different angiogenic and immune biomarkers to gain insights into the mechanisms of action of maintenance therapy in children with ALL. We thus monitored circulating endothelial cells (CEC), endothelial progenitor cells (EPC) and endothelial microparticles (EMP), pro-angiogenic factors (VEGF, VEGFR-1 and Ang-2), anti-angiogenic factor thrombospondin-1 (THBS1) and regulatory T lymphocytes (Treg) in 47 children with ALL during the maintenance phase of their treatment (at treatment initiation and after 6, 12 and 18 months)...
September 8, 2015: Oncotarget
Jun-Eui Park, Jinah Jang, Ji-Hye Choi, Mi-Sun Kang, Yun-Ju Woo, Young-Rim Seong, Chan-Bum Choi, Hye-Soon Lee, Sang-Cheol Bae, Yong-Soo Bae
We have previously demonstrated that semimature dendritic cell- (smDC-) based immunotherapy is effective for the treatment of collagen-induced arthritis (CIA) prior to disease onset. In the present study, we examined the efficacy of combination therapy with smDCs and methotrexate (MTX) in advanced CIA with a score of 2-3. Combination therapy with low-dose MTX and type II collagen- (CII-) pulsed smDCs (CII-smDCs) was more effective in inhibiting disease progression than high or low-dose MTX alone or a combination of high dose MTX and CII-smDCs...
2015: Journal of Immunology Research
Eun Wha Choi, Il Seob Shin, Ji Woo Song, MinJae Lee, Tae Won Yun, Jehoon Yang, Kyu-Sil Choi, Sung-Joo Kim
CTLA4Ig has therapeutic potential for rheumatoid arthritis patients unresponsive to methotrexate (MTX) or TNF-α blockers. However, recombinant CTLA4Ig proteins are short acting and expensive. Adipose tissue-derived mesenchymal stem cells (ASCs) present an ideal stem cell source for practical regenerative medicine due to their abundant availability and their beneficial properties including immunomodulation, homing activity, paracrine effects, and differentiation ability. Therefore, we aimed to determine whether CTLA4Ig and human ASCs show synergistic effects on immunomodulation and clinical improvement of sustained severe rheumatoid arthritis in a mouse model...
2016: Cell Transplantation
Maja Bulatović Ćalasan, Sebastiaan J Vastert, Rianne C Scholman, Frederik Verweij, Mark Klein, Nico M Wulffraat, Berent J Prakken, Femke van Wijk
OBJECTIVE: The balance between Treg and effector T cells (Teff) is crucial for immune regulation in JIA. How MTX, the cornerstone treatment in JIA, influences this balance in vivo is poorly elucidated. The aim of this study was to investigate quantitative and qualitative effects of MTX on Treg and Teff in JIA patients during MTX treatment. METHODS: Peripheral blood samples were obtained from JIA patients at the start of MTX and 3 and 6 months thereafter. Treg numbers and phenotypes were determined by flow cytometry and suppressive function in allogeneic suppression assays...
September 2015: Rheumatology
Kyu-Hyung Park, Chin Hee Mun, Mi-Il Kang, Sang-Won Lee, Soo-Kon Lee, Yong-Beom Park
Mesenchymal stem cells (MSCs) have immune modulatory properties. We investigated the potential therapeutic effects of human bone marrow (BM)-, adipose tissue (AD)-, and cord blood (CB)-derived MSCs in an experimental animal model of rheumatoid arthritis (RA) and explored the mechanism underlying immune modulation by MSCs. We evaluated the therapeutic effect of clinically available human BM-, AD-, and CB-derived MSCs in DBA/1 mice with collagen-induced arthritis (CIA). CIA mice were injected intraperitoneally with three types of MSCs...
2016: Cell Transplantation
Zhao Xiao, Long Juan, Yun Song, Zhang Zhijian, Jin Jing, Yu Kun, Hao Yuna, Dai Dongfa, Ding Lili, Tan Liuxin, Liang Fei, Liu Nan, Yuan Fang, Sun Yuying, Xi Yongzhi
A major challenge in the development of effective therapies for rheumatoid arthritis (RA) is finding a method for the specific inhibition of the inflammatory disease processes without the induction of generalized immunosuppression. Of note, the development of therapeutic DNA vaccines and boosters that may restore immunological tolerance remains a high priority. pcDNA-CCOL2A1 is a therapeutic DNA vaccine encoding chicken type II collagen(CCII). This vaccine was developed by our laboratory and has been shown to exhibit efficacy comparable to that of the current "gold standard" treatment, methotrexate (MTX)...
2015: Human Vaccines & Immunotherapeutics
Raphael Sanches Peres, Foo Y Liew, Jhimmy Talbot, Vanessa Carregaro, Rene D Oliveira, Sergio L Almeida, Rafael F O França, Paula B Donate, Larissa G Pinto, Flavia I S Ferreira, Diego L Costa, Daniel P Demarque, Dayana Rubio Gouvea, Norberto P Lopes, Regina Helena C Queiroz, Joao Santana Silva, Florencio Figueiredo, Jose Carlos Alves-Filho, Thiago M Cunha, Sérgio H Ferreira, Paulo Louzada-Junior, Fernando Q Cunha
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by joint destruction and severe morbidity. Methotrexate (MTX) is the standard first-line therapy of RA. However, about 40% of RA patients are unresponsive to MTX treatment. Regulatory T cells (Tregs, CD4(+)CD25(+)FoxP3(+)) are thought to play an important role in attenuating RA. To investigate the role of Tregs in MTX resistance, we recruited 122 RA patients (53 responsive, R-MTX; 69 unresponsive, UR-MTX) and 33 healthy controls. Three months after MTX treatment, R-MTX but not UR-MTX showed higher frequency of peripheral blood CD39(+)CD4(+)CD25(+)FoxP3(+) Tregs than the healthy controls...
February 24, 2015: Proceedings of the National Academy of Sciences of the United States of America
Adam P Cribbs, Alan Kennedy, Henry Penn, Parisa Amjadi, Patricia Green, Jordan E Read, Fionula Brennan, Bernard Gregory, Richard O Williams
OBJECTIVE: We have previously shown, in a cohort of untreated rheumatoid arthritis (RA) patients, that the suppressive function of Treg cells is defective. However, other studies in cohorts of patients with established RA have shown that Treg cell function is normal. We hypothesized that treatment may restore Treg cell function and lead to reduced disease activity. The aim of this study was to investigate whether treatment with methotrexate (MTX) can result in epigenetic changes that lead to restoration of the Treg cell suppressive function in RA...
May 2015: Arthritis & Rheumatology
Agata Kosmaczewska, Lidia Ciszak, Jerzy Swierkot, Aleksandra Szteblich, Katarzyna Kosciow, Irena Frydecka
Interleukin-2 (IL-2) has been suggested to control Treg/Th17 balance. Recently, we reported a relationship of rheumatoid arthritis (RA) activity/progression with irreversible systemic Treg and Th1 defects including serum IL-2 shortage. Herein, we explore the role of in vitro stimulation with rIL-2 in the observed immune alterations reversal. Patients with stable or progressive RA were assigned to methotrexate (MTX) group or to TNF-alpha inhibitors (iTNF) group, respectively. Flow cytometric analyses were performed before and after 6 months of treatment...
April 2015: Inflammation
G Guggino, A Giardina, A Ferrante, G Giardina, C Schinocca, G Sireci, F Dieli, F Ciccia, G Triolo
The aim of our study was to evaluate methotrexate (MTX) and methylprednisolone (MP) effect on peripheral Th17 and Treg subsets in patients with rheumatoid arthritis (RA). We enrolled 15 patients (10 early RA and 5 long-standing disease) with active RA and 10 age-matched healthy donors as controls. Frequencies of Th17 and Treg were quantified using flow cytometry before and after in vitro addition of MTX, MP or both drugs. Our results showed a reduction in the overall Th17 population followed by an increase in Th17 IL-10(+) and Treg, after in vitro treatment of PBMCs with the drugs in patients with early RA...
January 2015: Rheumatology International
A Picchianti Diamanti, M M Rosado, M Scarsella, V Germano, E Giorda, S Cascioli, B Laganà, R D'Amelio, R Carsetti
The use of biological agents combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients has strongly improved disease outcome. In this study, the effects of abatacept on the size and function of circulating B and T cells in RA patients not responding to anti-tumour necrosis factor (TNF)-α have been analysed, with the aim of identifying immunological parameters helpful to choosing suitable tailored therapies. We analysed the frequency of peripheral B and T cell subsets, B cell function and T regulatory cell (Treg ) inhibitory function in 20 moderate/severe RA patients, according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, primary non-responders to one TNF-α blocking agent, who received abatacept + MTX...
September 2014: Clinical and Experimental Immunology
Agata Kosmaczewska, Jerzy Swierkot, Lidia Ciszak, Aleksandra Szteblich, Agnieszka Chrobak, Lidia Karabon, Anna Partyka, Jacek Szechinski, Piotr Wiland, Irena Frydecka
Systemic immune defects might reflect severely dysregulated control of chronic inflammation related to disease progression. Th17/Treg cell imbalance has been demonstrated to be involved in rheumatoid arthritis (RA) pathogenesis. Despite controversial results, a growing anti-inflammatory role in this process has been recently attributed to Th1 responses. The aim of the study was to estimate the extent of Th1/Th17/Treg imbalance in peripheral blood (PB) of patients with short- and long-term RA in relation to cytokine milieu and its reversal after therapy with methotrexate and/or TNF inhibitors, respectively...
February 2014: Rheumatology International
Xiaoyang Yu, Caihong Wang, Jing Luo, Xiangcong Zhao, Lixing Wang, Xiaofeng Li
Immune disorder is considered the main pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA). The balance of the two special subsets of CD4⁺T cells, T helper cell 17 (Th17), and Regulator T cell (Treg) is the key factor of maintaining a normal immune response. Dendritic cells (DCs), which are the most powerful antigen-presenting cells, play an important role in regulating the balance of Th17 and Treg. The combination of disease modifying antirheumatic drugs (DMARDs) is an important strategy of RA therapy...
2013: Clinical & Developmental Immunology
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