Search results for "Lymph"
showing 10 items of 4590 documents
Enhanced dendritic cell maturation by TNF-alpha or cytidine-phosphate-guanosine DNA drives T cell activation in vitro and therapeutic anti-tumor immu…
2000
Abstract Dendritic cells (DC) manipulated ex vivo can induce tumor immunity in experimental murine tumor models. To improve DC-based tumor vaccination, we studied whether DC maturation affects the T cell-activating potential in vitro and the induction of tumor immunity in vivo. Maturation of murine bone marrow-derived DC was induced by GM-CSF plus IL-4 alone or by further addition of TNF-α or a cytidine-phosphate-guanosine (CpG)-containing oligonucleotide (ODN-1826), which mimics the immunostimulatory effect of bacterial DNA. Flow cytometric analysis of costimulatory molecules and MHC class II showed that DC maturation was stimulated most by ODN-1826, whereas TNF-α had an intermediate effec…
Suppressive effects of C3b on monocyte-dependent T cell proliferation.
1987
The effect of C3b treatment of human monocytes on secondary antigen-dependent T cell response was studied. When antigen-specific T cell blasts were cultivated together with C3b-treated monocytes the proliferative response was inhibited in a dose-dependent fashion. This suppressive effect was specific for C3b because heat-inactivated C3b or buffer alone had no influence on T cell proliferation. In part, this suppressive effect is mediated through a C3b-induced decreased expression of class II antigens on the surface of treated monocytes, but another suppressive mechanism exists because the C3b pretreatment of monocytes also led to an inhibition of the proliferative response in a class II ant…
HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification
2014
Summary The recent HIV-1 vaccine failures highlight the need to better understand virus-host interactions. One key question is why CD8+ T cell responses to two HIV-Gag regions are uniquely associated with delayed disease progression only in patients expressing a few rare HLA class I variants when these regions encode epitopes presented by ∼30 more common HLA variants. By combining epitope processing and computational analyses of the two HIV subtypes responsible for ∼60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions at subtype-specific motifs. Multiple HLA variants presenting epitopes situated next to a giv…
Intrahepatic myeloid-cell aggregates enable local proliferation of CD8+T cells and successful immunotherapy against chronic viral liver infection
2013
Chronic infection is difficult to overcome because of exhaustion or depletion of cytotoxic effector CD8(+) T cells (cytotoxic T lymphoytes (CTLs)). Here we report that signaling via Toll-like receptors (TLRs) induced intrahepatic aggregates of myeloid cells that enabled the population expansion of CTLs (iMATEs: 'intrahepatic myeloid-cell aggregates for T cell population expansion') without causing immunopathology. In the liver, CTL proliferation was restricted to iMATEs that were composed of inflammatory monocyte-derived CD11b(+) cells. Signaling via tumor-necrosis factor (TNF) caused iMATE formation that facilitated costimulation dependent on the receptor OX40 for expansion of the CTL popu…
Tumors as elusive targets of T-cell-based active immunotherapy.
2003
The understanding of tumor-host interactions remains elusive despite significant progress in the identification of tumor antigens (TAs) recognized by autologous T cells. In particular, most human tumors do not regress and continue to grow in spite of spontaneous or immunization-induced immune responses demonstrated in circulating lymphocytes. Indeed, systemic immune responses might insufficiently address the complexity of tumor-host interactions because of factors, such as (1) the lack of productive T-cell receptor (TCR) engagement with epitope owing to qualitative and/or quantitative defects in the generation and maintenance of the immune response, (2) insufficient costimulation provided b…
Efficient homologous prime-boost strategies for T cell vaccination based on virus-like particles.
2005
Induction of high frequencies of specific T cells by vaccination requires prime-boost regimens. To reach optimal immune responses, it is necessary to use different vectors for priming and boosting as e.g. DNA vaccination followed by boosting with a recombinant viral vector. Here, we show that vaccines based on virus-like particles (VLP) displaying peptide epitopes are equally effective to induce CTL responses if used in a homologous or heterologous prime-boost setting. Strikingly, high frequencies (>20% of CD8(+) cells) of protective CTL could be induced and maintained by weekly injection of VLP. Thus, the use of VLP may avoid the requirement for complicated heterologous prime-boost regi…
Phenotypical and Functional Alteration of γδ T Lymphocytes in COVID-19 Patients: Reversal by Statins
2022
(1) Background: statins have been considered an attractive class of drugs in the pharmacological setting of COVID-19 due to their pleiotropic properties and their use correlates with decreased mortality in hospitalized COVID-19 patients. Furthermore, it is well known that statins, which block the mevalonate pathway, affect γδ T lymphocyte activation. As γδ T cells participate in the inflammatory process of COVID-19, we have investigated the therapeutical potential of statins as a tool to inhibit γδ T cell pro-inflammatory activities; (2) Methods: we harvested peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild clinical manifestatio…
Inhibition of Transcription Factors by Plant-Derived Compounds and their Implications in Inflammation and Cancer
2009
Inflammation is a general term used to describe various pathological processes with diverse causes that can include infection, trauma, or an autoimmune response. Due to its many causes, the inflammatory response involves multiple and varied mediators, including vasoactive amines, free radicals, and both lipidic and peptidic mediators. Medicinal plants and the compounds derived from them are a good source of new and specific inhibitors of the inflammatory process. The past decade has witnessed many important discoveries in this field, with new findings challenging the more traditional views of pharmacologists. Various studies, for example, have demonstrated the positive effects of plant-deri…
An innate cell-mediated, murine ulcerative colitis-like syndrome in the absence of nuclear factor of activated T cells.
2004
Abstract Background & Aims: Nuclear factor of activated T cells transcription factors plays a central role in immunity by regulating the expression of multiple cytokines and other regulatory molecules, many of which have been heavily implicated in the pathogenesis of inflammatory bowel disease. However, few studies have directly investigated the nuclear factor of activated T cells proteins in inflammatory bowel disease. We describe here a specific role for nuclear factor of activated T cells c2 in the pathogenesis of murine inflammatory bowel disease. Methods: Mice deficient for nuclear factor of activated T cells c2, recombinase activating gene-2, or both and transgenic or nontransgenic fo…
CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.
2008
T regulatory (Treg) cells play a role in the suppression of immune responses, thus serving to induce tolerance and control autoimmunity. Here, we explored whether Treg cells influence the immediate hypersensitivity response of mast cells (MCs). Treg cells directly inhibited the FcεRI-dependent MC degranulation through cell-cell contact involving OX40-OX40L interactions between Treg cells and MCs, respectively. When activated in the presence of Treg cells, MCs showed increased cyclic adenosine monophosphate (cAMP) concentrations and reduced Ca2+ influx, independently of phospholipase C (PLC)-γ2 or Ca2+ release from intracellular stores. Antagonism of cAMP in MCs reversed the inhibitory effec…