Search results for "suppressive"

Immunosuppressive treatment for systemic sclerosis—Therapeutic challenges during the COVID ‐19 pandemic

2020

Splenic Littoral Cell Hemangioendothelioma in a Patient With Crohn's Disease Previously Treated With Immunomodulators and Anti-TNF Agents: A Rare Tum…

2011

Th e risk of malignancy in Crohn ’ s disease (CD) has been well described. Moreover, immunomodulators, uch as azathioprine (AZA) and 6-mercaptopurine (6-MP), and biological agents, such as infl iximab and adalimumab, may promote carcinogenesis ( 1 – 3 ). Splenic littoral cell tumors are recently described tumors of vascular origin composed of endothelial cells, with typical microscopic and immunohistochemical features of splenic sinus lining cells ( 4 ). Clinical findings are not specific, and outcome is unpredictable but usually benign, although a few cases with a malignant behavior have been reported ( 5,6 ). We report a 58-year-old Caucasian man with a long history of ileocolonic CD.

Recomendaciones en el manejo de la pandemia por coronavirus SARS-CoV-2 (Covid-19) en pacientes con trasplante renal

2020

The SARS-CoV-2 (Covid-19) coronavirus pandemic is evolving very quickly and means a special risk for both immunosuppressed and comorbid patients. Knowledge about this growing infection is also increasing although many uncertainties remain, especially in the kidney transplant population. This manuscript presents a proposal for action with general and specific recommendations to protect and prevent infection in this vulnerable population such as kidney transplant recipients. Resumen: La pandemia por coronavirus SARS-CoV-2 (Covid-19) está evolucionando de manera muy rápida y representa un riesgo especial en pacientes inmunodeprimidos y con comorbilidades añadidas. El conocimiento sobre esta in…

Physiological and metabolic actions of mycophenolate mofetil on cultured newborn rat cardiomyocytes in normoxia and in simulated ischemia

2004

Mycophenolate mofetil (MMF) is a new immunosuppressive drug used to reduce acute rejection after heart transplantation. As with other immunosuppressive drugs, MMF therapy is associated with several adverse effects. However, the direct effects of MMF on myocardial tissue has not been yet evaluated. The aim of the work was thus to evaluate the effects of MMF on isolated cardiomyocytes (CM) in normal conditions and in an in vitro model of simulated ischemia (SI; substrate-free hypoxia) and reperfusion (R; reoxygenation). Myocyte-enriched cultures were prepared from newborn rat heart ventricles. The transmembrane potentials were recorded using conventional microelectrodes and the cell contracti…

The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

2013

The Microbiota Makes for Good Therapy The gut microbiota has been implicated in the development of some cancers, such as colorectal cancer, but—given the important role our intestinal habitants play in metabolism—they may also modulate the efficacy of certain cancer therapeutics. Iida et al. (p. 967 ) evaluated the impact of the microbiota on the efficacy of an immunotherapy [CpG (the cytosine, guanosine, phosphodiester link) oligonucleotides] and oxaliplatin, a platinum compound used as a chemotherapeutic. Both therapies were reduced in efficacy in tumor-bearing mice that lacked microbiota, with the microbiota important for activating the innate immune response against the tumors. Viaud et…

Serotherapy with thymoglobulin and alemtuzumab differentially influences frequency and function of natural killer cells after allogeneic stem cell tr…

2007

Although thymoglobulin and alemtuzumab are frequently used in hematopoietic stem cell transplantation (HSCT), little is known of their effects on NK cells, which mediate important functions in post-transplantation immunology. In the present study, we determined NK cell death in vitro using propidium iodide and Annexin V. The NK cell activity in 34 patients at day +30 after allogeneic HSCT was assessed using the CD107a assay. Alemtuzumab and thymoglobulin were similarly very potent in inducing NK cell death in vitro. Even in low concentrations (1 microg/ml) the antibodies induced apoptosis and necrosis in a relevant percentage of NK cells (30%). However, the number of tumor reactive (CD107a+…

SARS-CoV-2-specific Cell-mediated Immunity in Kidney Transplant Recipients Recovered From COVID-19.

2021

BACKGROUND: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown. METHODS: We enumerated SARS-CoV-2-specific interferon-I³-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6. RESULTS: Detectable (≥0.1…

Dimethyl fumarate treatment restrains the antioxidative capacity of T cells to control autoimmunity

2021

Abstract Dimethyl fumarate, an approved treatment for relapsing-remitting multiple sclerosis, exerts pleiotropic effects on immune cells as well as CNS resident cells. Here, we show that dimethyl fumarate exerts a profound alteration of the metabolic profile of human CD4+ as well as CD8+ T cells and restricts their antioxidative capacities by decreasing intracellular levels of the reactive oxygen species scavenger glutathione. This causes an increase in mitochondrial reactive oxygen species levels accompanied by an enhanced mitochondrial stress response, ultimately leading to impaired mitochondrial function. Enhanced mitochondrial reactive oxygen species levels not only result in enhanced T…

CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes

2003

Azathioprine and its metabolite 6-mercaptopurine (6-MP) are immunosuppressive drugs that are used in organ transplantation and autoimmune and chronic inflammatory diseases such as Crohn disease. However, their molecular mechanism of action is unknown. In the present study, we have identified a unique and unexpected role for azathioprine and its metabolites in the control of T cell apoptosis by modulation of Rac1 activation upon CD28 costimulation. We found that azathioprine and its metabolites induced apoptosis of T cells from patients with Crohn disease and control patients. Apoptosis induction required costimulation with CD28 and was mediated by specific block- ade of Rac1 activation thro…

Azathioprine suppresses ezrin-radixin-moesin-dependent T cell-APC conjugation through inhibition of Vav guanosine exchange activity on rac proteins

2006

Abstract We have shown recently that the azathioprine metabolite 6-Thio-GTP causes immunosuppression by blockade of GTPase activation in T lymphocytes. In the present study, we describe a new molecular mechanism by which 6-Thio-GTP blocks GTPase activation. Although 6-Thio-GTP could bind to various small GTPases, it specifically blocked activation of Rac1 and Rac2 but not of closely related Rho family members such as Cdc42 and RhoA in primary T cells upon stimulation with αCD28 or fibronectin. Binding of 6-Thio-GTP to Rac1 did not suppress Rac effector coupling directly but blocked Vav1 exchange activity upon 6-Thio-GTP hydrolysis, suggesting that 6-Thio-GTP loading leads to accumulation of…