Search results for "chemical and pharmacologic phenomena"
showing 10 items of 616 documents
The Transcription Factor T-bet Is Induced by IL-15 and Thymic Agonist Selection and Controls CD8αα+ Intraepithelial Lymphocyte Development
2014
Summary CD8αα + intraepithelial lymphocytes (IELs) are instrumental in maintaining the epithelial barrier in the intestine. Similar to natural killer cells and other innate lymphoid cells, CD8αα + IELs constitutively express the T-box transcription factor T-bet. However, the precise role of T-bet for the differentiation or function of IELs is unknown. Here we show that mice genetically deficient for T-bet lacked both TCRαβ + and TCRγδ + CD8αα + IELs and thus are more susceptible to chemically induced colitis. Although T-bet was induced in thymic IEL precursors (IELPs) as a result of agonist selection and interleukin-15 (IL-15) receptor signaling, it was dispensable for the generation of IEL…
Effects of in vitro treatment with fluticasone propionate on natural killer and lymphokine-induced killer activity in asthmatic and healthy individua…
2001
Background: Topical corticosteroids are beneficial in the treatment of allergic respiratory disorders; they exert effects on a number of cells involved in allergic inflammatory reactions. On the other hand, major histocompatibility complex (MHC)-unrestricted cytotoxicity (i.e., natural killer [NK] cell activity) may play a role in the inflammatory allergic reaction. The objective was to gain insight into the mechanisms of the therapeutic effects of fluticasone propionate (FP), an inhaled corticosteroid used in asthma and rhinitis therapy. Therefore, we evaluated the NK and lymphokine-activated killer (LAK) activity of effector cells in vitro treated or not with FP. Methods: Evaluations were…
IgG1 anti-epidermal growth factor receptor antibodies induce CD8-dependent antitumor activity
2014
Anti-EGFR monoclonal antibodies (mAb) like Cetuximab are commonly used for treatment of EGFR+ solid tumors mainly by exerting their therapeutic effect through inhibition of signal transduction. Additionally, IgG1 is a potent mediator of antibody-dependent cytotoxicity (ADCC). In case of the IgG1, Cetuximab induction of ADCC in vivo is controversially discussed. In our study, we investigated the efficiency of Cetuximab-mediated ADCC in a humanized mouse tumor model in vivo and analyzed the contribution of immunologic processes toward antitumor activity. Therefore, we used immunodeficient NOD/Scid mice transgenic for human MHC class I molecule HLA-A2 and adoptively transferred human HLA-A2+ P…
K Cell Activity of Normal and Chronic Lymphocytic Leukaemia Lymphocytes: Association with Lymphocytes bearing Receptors for Human C3b
1977
Surface properties of effector cells in antibody-dependent cell mediated cytotoxicity (ADCC) are at present under intensive investigation. Among these cells a lymphocyte population (K cells) has been described with receptors for the Fc portion of IgG (4), receptors for complement (11) and lacking receptors for sheep red blood cells (SRBC) and surface immunoglobulin (13). The purpose of the present study was to investigate more thoroughly the relationship between K cell activity in ADCC and cells bearing receptors for C3b and C3d.
Two-site ELISA for quantification of the terminal C5b-9 complement complex in plasma
1993
Abstract A quantitative ELISA procedure using monoclonal and polyclonal antibodies against neoantigens of the terminal C5b-9 complement complex has been developed. The ELISA was demonstrated to be both sensitive and reproducible. The normal range for C5b-9 determinations, defined as 2.5–97.5% interval of the values obtained in 76 healthy blood donors, was 3.12–10.3 AU/ml. The presence of rheumatoid factor did not affect the determination of C5b-9 as demonstrated by immunoabsorption studies.
Generation of monoclonal antibodies against human regulatory T cells.
2009
Abstract Natural CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) control the activation of the immune system and therefore have become a major area of research in immunology. The generation of monoclonal antibodies against human Tregs offers the possibility to discover novel Treg-specific or Treg-associated surface markers and to identify targets for a therapeutic modulation of Tregs. Here we present a methodology optimized to efficiently induce and select mAb against human Tregs by repeated immunization of mice with Tregs from a single donor and a differential two-step flow cytometry-based hybridoma screening procedure.
Induction of tolerogenic DCs: ‘you are what you eat’
2003
Abstract Dendritic cells (DCs) take up antigens using antigen receptors that can be divided into three major classes: C-type lectins, integrins and Fc receptors. These receptors facilitate effective presentation of MHC–peptide complexes to T cells, resulting in the induction of immune responses. However, we discuss recent evidence that some receptors also cause induction of tolerance. Signaling motifs within the receptors either block maturation of DCs or induce signals that render DCs tolerogenic. These DCs then either induce regulatory T cells or cause deletion of effector T cells, resulting in the induction of tolerance. Antigen receptors expressed by DCs might therefore have an importan…
Targeting p53, hdm2, and CD19: vaccination and immunologic strategies.
2000
Peptides presented by class I major histocompatibility complex (MHC) molecules and derived from normal self-proteins that are expressed at elevated levels by cells from a variety of human (Hu) malignancies provide, in theory, potential target antigens for a broad-spectrum, cytotoxic T lymphocyte (CTL)-based immunotherapy of cancer and hematologic malignancies. However, as such tumor- and leukemia-associated self-proteins are also expressed at low levels in some types of normal tissues, such as thymus, spleen and lymphohemopoietic cells, these self-MHC-self-peptide complexes may also represent thymic and/or peripheral tolerogens, thereby preventing immune responses. This is particularly true…
Separation of T-cell-stimulating activity from streptococcal M protein
1992
The superantigenic properties of M protein type 5 of Streptococcus pyogenes have been implicated as an important pathogenicity factor in streptococcal autoimmune diseases. Here we show that after a single purification step by affinity chromatography on immobilized albumin or fibrinogen, M protein has no mitogenic activity for T cells. We demonstrate that the superantigenicity of M proteins of type 5 and type 1 is due to contamination with the highly potent pyrogenic exotoxins of S. pyogenes in the range of 0.1 to 0.01%. These results raise a general caveat for work with these extremely active T-cell mitogens, because the mitogenicity of other streptococcal or staphylococcal proteins could b…
The enemy in you: the interdependency of the localisation and antigenicity of proteins
2009
The subcellular localisation of protein components should be important for their antigenicity. This assumption is derived from the concept of MHC restriction, where CD4 and CD8 T lymphocytes can only interact with MHC II and MHC I surface receptors, respectively. If this mechanism applies, however, then intracellular components should have immunogenic effects mediated by MHC II and CD4 T lymphocytes as soon as they enter the extracellular space. Conversely, extracellular components should generate an immune response that is mediated by MHC I and CD8 lymphocytes when they breach the intracellular space and when they exceed a critical concentration. In this study, these hypotheses were invest…