Search results for "Tumor necrosis factor."
showing 10 items of 848 documents
Differential effects of IL-10 on proliferation and cytokine production of human gamma/delta and alpha/beta T cells.
1994
Gamma/delta TCR bearing T lymphocytes represent a T-cell subset whose functional relevance remains unclear. Nevertheless these T cells may play a role in the early immune response against bacteria. Until now the regulatory mechanisms on this response have not been investigated. The study described here evaluated the immunoregulatory effects of Interleukin-10 on gamma/delta and alpha/beta TCR-positive T-cell clones and freshly isolated peripheral-blood mononuclear cells (PBMC). IL-10 has been shown previously to inhibit lectin and antigen-induced proliferation and cytokine production by alpha/beta T cells. The results outlined below show that rhIL-10 strongly inhibits lectin-induced producti…
A Key Regulatory Role of the Transcription Factor NFATc2 in Bronchial Adenocarcinoma via CD8+ T Lymphocytes
2009
AbstractThe Ca2+-regulated calcineurin/nuclear factor of activated T cells (NFAT) cascade controls alternative pathways of T-cell activation and peripheral tolerance. Here, we describe reduction of NFATc2 mRNA expression in the lungs of patients with bronchial adenocarcinoma. In a murine model of bronchoalveolar adenocarcinoma, mice lacking NFATc2 developed more and larger solid tumors than wild-type littermates. The extent of central tumor necrosis was decreased in the tumors in NFATc2(−/−) mice, and this finding was associated with reduced tumor necrosis factor-α and interleukin-2 (IL-2) production by CD8+ T cells. Adoptive transfer of CD8+ T cells of NFATc2(−/−) mice induced transforming…
The gp130-stimulating designer cytokine hyper-IL-6 promotes the expansion of human hematopoietic progenitor cells capable to differentiate into funct…
2000
Abstract Objective . Hyper-IL-6, a fusion protein of interleukin-6 and its specific receptor, together with stem cell factor leads to the proliferation of primitive hematopoietic progenitor cells. Based on these findings, the current study examined whether hyper-IL-6 promotes the growth of precursor cells that can be further differentiated into dendritic cells in the presence of additional cytokines. Methods . Dendritic cell cultures were generated from CD34 + hematopoietic progenitor cells derived either from bone marrow or from peripheral blood. CD34 + cells were cultured in the presence of cytokines for 2 weeks and then used for phenotyping and T-cell stimulation assays. Results . Hyper-…
Liver-infiltrating and circulating CD4+ T cells in chronic hepatitis C: immunodominant epitopes, HLA-restriction and functional significance.
2008
The aim was to assess the specificity and functional significance of liver-infiltrating and peripheral blood T cells in chronic hepatitis C. Peripheral blood mononuclear cells hepatitis C virus from 50 of 58 (86.2%) patients with chronic hepatitis C virus infection and 6 of 28 (21.4%) controls showed a proliferative T cell response to at least one of 16 synthetic peptides covering highly conserved regions of the core, envelope (El) and non-structural regions (NS4) of hepatitis C virus. However, six immunodominant peptides were exclusively recognized by the proliferating blood mononuclear cells from 46 patients with chronic hepatitis C virus infection (79.3%). Fine specificity and HLA-restri…
Rapid identification and sorting of viable virus-reactive CD4+ and CD8+ T cells based on antigen-triggered CD137 expression
2008
Abstract Current methods for the detection and isolation of antigen-specific CD4 + and CD8 + T cells require the availability of peptide/MHC multimers or are restricted to cells that produce cytokines after antigen contact. Here we show that de novo cell surface expression of the TNF-receptor family member CD137 (4-1BB) identifies recently activated, but not resting, human CD4 + and CD8 + memory T cells. Maximum CD137 expression level is uniformly observed in both T-cell subsets at 24h after stimulation with antigen. In experiments with CMV and EBV-reactive T cells, we confirmed the specificity of CD137 expression by co-staining with peptide/HLA tetramers. Substantial proportions of CD137 +…
Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines.
2006
AbstractIn HLA-incompatible hematopoietic stem cell transplantation, alloreactive donor T cells recognizing recipient mismatch HLA cause severe graft-versus-host disease (GVHD). Strategies allowing the selective depletion of alloreactive T cells as well as the enhancement of graft-versus-malignancy immunity would be beneficial. We generated donor CD8 T-cell lines in vitro using allogeneic recipient cells mismatched at a single HLA class I allele or haplotype as stimulators. Recipient cells were obtained from acute myeloid leukemias, renal-cell carcinomas, and CD40L-induced B lymphoblasts. Resulting alloreactive T cells were activated by incubating day 21 T-cell cultures with HLA-mismatch tr…
Regulatory activity of human CD4 CD25 T cells depends on allergen concentration, type of allergen and atopy status of the donor.
2005
Regulatory CD4+ CD25+ FoxP3-positive T cells (Treg) are functional in most atopic patients with allergic rhinitis and are able to inhibit T helper type 1 (Th1) and Th2 cytokine production of CD4+ CD25- T cells. This study was designed to analyse the following additional aspects: influence of allergen concentration, influence of the type of allergen, and influence of the atopy status of the donor on the strength of the regulatory activity. CD4+ CD25- T cells from healthy non-atopic controls or from grass-pollen-allergic or wasp-venom-allergic donors were stimulated alone or in the presence of Treg with autologous mature monocyte-derived dendritic cells which were pulsed with different concen…
Is TNF-α really involved in giant cell arteritis pathogenesis?
2013
Giant cell arteritis (GCA) is the most frequent vasculitis in people >50 years, and glucocorticoids (GC) remain the cornerstone of the treatment. However, this long-term treatment is responsible for numerous GC-related complications.1 Thus, reliable GC-sparing drugs need to be explored. Seror et al 2 have recently reported the inefficacy of adalimumab, a humanised anti-TNF-α therapy, as a GC-sparing drug in the treatment of GCA. These clinical results contrast with previous studies reporting a production of TNF-α by giant cells and macrophages in GCA lesions.3 However, recent advance in the knowledge of GCA pathogenesis have shown that macrophages and giant cells are not involved in the fir…
Antibodies against tumor necrosis factor (TNF) induce T-cell apoptosis in patients with inflammatory bowel diseases via TNF receptor 2 and intestinal…
2011
Background & Aims The anti–tumor necrosis factor (TNF) antibodies infliximab, adalimumab, and certolizumab pegol have proven clinical efficacy in Crohn's disease. Here, we assessed the effects of anti-TNF antibodies on apoptosis in inflammatory bowel disease (IBD). Methods CD14 + macrophages and CD4 + T cells were isolated from peripheral blood and lamina propria mononuclear cells from patients with IBD and control patients. Cell surface markers and apoptosis were assessed by immunohistology and fluorescence-activated cell sorting techniques. Results Lamina propria CD14 + macrophages showed significantly more frequent and higher membrane-bound TNF (mTNF) expression than CD4 + T cells in IBD…
Methotrexate specifically modulates cytokine production by T cells and macrophages in murine collagen-induced arthritis (CIA): a mechanism for methot…
1999
SUMMARYImmunosuppressive therapy with methotrexate (MTX) has been established as effective treatment for patients with rheumatoid arthritis. To analyse the therapeutic potential and mechanisms of action of MTX, we determined serum cytokine levels and cytokine production by splenic T cells and macrophages in untreated and MTX-treated mice. Furthermore, we assessed the role of MTX in a murine model of experimental arthritis induced by collagen type II (CIA). MTX reduced spontaneous and IL-15-induced tumour necrosis factor (TNF) production by splenic T cells but not by macrophages from healthy mice in vitro in a dose-dependent manner. In contrast, interferon-gamma (IFN-γ) production was less s…