Search results for "INTERLEUKIN-2"
showing 10 items of 269 documents
Interferon-α Suppresses cAMP to Disarm Human Regulatory T Cells
2013
Abstract IFN-α is an antineoplastic agent in the treatment of several solid and hematologic malignancies that exerts strong immune- and autoimmune-stimulating activity. However, the mechanisms of immune activation by IFN-α remain incompletely understood, particularly with regard to CD4+CD25highFoxp+ regulatory T cells (Treg). Here, we show that IFN-α deactivates the suppressive function of human Treg by downregulating their intracellular cAMP level. IFN-α–mediated Treg inactivation increased CD4+ effector T-cell activation and natural killer cell tumor cytotoxicity. Mechanistically, repression of cAMP in Treg was caused by IFN-α–induced MAP–ERK kinase (MEK)/extracellular signal-regulated ki…
P38 MAP Kinase Signaling Is Required for the Conversion of CD4+CD25− T Cells into iTreg
2008
CD4+CD25+ regulatory T cells (Treg) are important mediators of immune tolerance. A subset of Treg can be generated in the periphery by TGF-beta dependent conversion of conventional CD4+CD25− T cells into induced Treg (iTreg). In chronic viral infection or malignancy, such induced iTreg, which limit the depletion of aberrant or infected cells, may be of pathogenic relevance. To identify potential targets for therapeutic intervention, we investigated the TGF-beta signaling in Treg. In contrast to conventional CD4+ T cells, Treg exhibited marked activation of the p38 MAP kinase pathway. Inhibition of p38 MAP kinase activity prevented the TGF-beta-dependent conversion of CD4+CD25− T cells into …
The role of Interleukin-2 during the activation of cytotoxic T-lymphocytes
1983
Der vorliegende Artikel stellt eine Ubersicht dar Uber die derzeitigen Vorstellungen des Zusammenwirkens zellularer und humoraler Faktoren, die zu T-Zell-vermittelten zytotoxischen Immunreaktionen fuhren. Da im Ablauf derartiger Immunreaktionen hormonahnliche Wachstumsfaktoren (interleukine) eine entscheidende Rolle spielen, liegt der Schwerpunkt der Diskussion auf der Beschreibung dieser Mediatoren; insbesondere wird die Bedeutung von Interleukin-2 (Il-2) diskutiert. Il-2 ist ein losliches, nicht antigenspezifisches Glykoprotein mit einem Molekulargewicht von 15 000 Dalton (humanes Il-2) bzw. 30 000 Dalton (murines Il-2). Es wird in vitro von T-Helfer-Lymphozyten sezerniert, die in der Mau…
Intraperitoneal administration of the anti-IL-23 antibody prevents the establishment of intestinal nematodes in mice
2018
AbstractPrevious studies have established that an increased Th-9 response creates a hostile environment for nematode parasites. Given that IL-23, a cytokine required for maintenance of the IL-17–secreting phenotype, has inhibitory effects on IL-9 production, we hypothesized that reducing circulating IL-23 by treatment with anti-IL-23 antibodies would reduce the establishment and development of parasitic intestinal nematodes. In this study, we show that animals treated with anti-IL-23 monoclonal antibodies showed a drastic reduction in the number of mouse pinworms (Aspiculuris tetraptera) recovered from the intestine (p < 0.001) at 23 days post-infection compared to the untreated animals.…
The complex alteration in the network of IL-17-type cytokines in patients with hereditary angioedema
2018
Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis during attack and remission state and n = 19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1β, IL-6, IL-10, granulocyte–macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-β) subtypes. Data indicate that there are variations of cytokine levels in HAE subjects compar…
Inflammatory activation and endothelial dysfunction markers in patients with permanent atrial fibrillation: A cross-sectional study
2020
In recent years a growing body of evidence supported the role of inflammation in the initiation, maintenance and outcome of atrial fibrillation (AF). Nevertheless, despite a large amount of information, whether AF or the underlying structural heart disease (SHD) is the cause of the inflammatory process is still under debate. We, therefore, sought to determine if the inflammatory process reflect an underlying disease or the arrhythmia 'per se'. We evaluated plasma levels of soluble Interleukin 2 Receptor Alpha (sIL-2Rα), TNF-α and IL-18 in 100 consecutive patients with permanent AF, (43 with a SHD and 57 without a SHD) compared to 121 age and sex-matched controls which had normal sinus rhyth…
Long-term pertussis-specific immunity after primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis …
2001
ABSTRACT The aim of this study was to compare pertussis-specific humoral and cellular immunity in children 5 years after a primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine (DTaP-HBV; InfanrixHepB; SmithKline Beecham) with immunity after natural infection. The subjects were 38 children aged 5 to 6 years who received DTaP-HBV at 3, 5, and 11 months of life and 21 subjects of similar ages and sex who acquired pertussis in the first year of life. Immunoglobulin G (IgG) antibody titers against Bordetella pertussis antigens, peripheral blood mononuclear cell-specific proliferation, and the secretion of cytokines were evaluated. Aft…
High dose inhalation interleukin-2 therapy for lung metastases in patients with malignant melanoma.
2000
BACKGROUND The lungs are a frequent site of metastasis in patients with melanoma, and this may cause respiratory problems in the terminal phase of the illness. Inhalation interleukin (IL)-2 therapy to the lung has been piloted and appears to be well tolerated. METHODS Twenty-seven patients were treated with single agent dacarbazine and concurrent high dose inhalation IL-2 36 million IU per day). The patients previously had progressed on chemotherapy, predominately dacarbazine-based regimens. Patients included those with American Joint Committee on Cancer Stage IV melanoma, predominately those with lung metastases, but patients with extrapulmonary metastases also were allowed on the study. R…
Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profil…
2011
Purpose Abnormal cytokine expression accompanies myelofibrosis and might be a therapeutic target for Janus-associated kinase (JAK) inhibitor drugs. This study describes the spectrum of plasma cytokine abnormalities in primary myelofibrosis (PMF) and examines their phenotypic correlates and prognostic significance. Patients and Methods Patients included in this study were required to have archived plasma, bone marrow biopsy, and cytogenetic information available at the time of first referral to the Mayo Clinic. Multiplex biometric sandwich immunoassay was used to measure plasma levels of 30 cytokines. Results In total, 127 PMF patients were studied; comparison with normal controls (n = 35) r…
Immune-modulating effects of the newest cetuximab-based chemoimmunotherapy regimen in advanced colorectal cancer patients.
2012
Cetuximab is a human-murine chimeric monoclonal antibody to the epidermal growth factor receptor, active for advanced colorectal cancer treatment in combination with chemotherapy. Cetuximab mainly acts by inhibiting epidermal growth factor receptor-mediated pathways in cancer cells; however, in the human host, its IgG1 backbone may offer additional antitumor activity that includes FcγRs-mediated antibody-dependent cell cytotoxicity, phagocytosis, cross priming, and tumor-specific T-cell-mediated immune response. These mechanisms are still under active investigation. At this purpose, we have performed an immunologic investigation in advanced colon cancer patients enrolled in an ongoing phase…