Search results for " t-lymphocytes"
showing 10 items of 495 documents
The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells
2015
The modification of proteins by ubiquitin has a major role in cells of the immune system and is counteracted by various deubiquitinating enzymes (DUBs) with poorly defined functions. Here we identified the ubiquitin-specific protease USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads and the regulatory molecule 14-3-3β. Caspase-dependent processing of USP8 occurred after stimulation of the TCR. T cell-specific deletion of USP8 in mice revealed that USP8 was essential for thymocyte maturation and upregulation of the gene encoding the cytokine receptor IL-7Rα mediated by the transcription factor Foxo1. Mice with T cell-specifi…
Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation
2009
Abstract The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell–derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17–producing T cel…
Neuroinflammation by cytotoxic T-lymphocytes impairs retrograde axonal transport in an oligodendrocyte mutant mouse.
2012
Mice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow tr…
Bacterial and viral infections and related inflammatory responses in chronic obstructive pulmonary disease
2021
Abstract In chronic obstructive pulmonary disease (COPD) patients, bacterial and viral infections play a relevant role in worsening lung function and, therefore, favour disease progression. The inflammatory response to lung infections may become a specific indication of the bacterial and viral infections. We here review data on the bacterial–viral infections and related airways and lung parenchyma inflammation in stable and exacerbated COPD, focussing our attention on the prevalent molecular pathways in these different clinical conditions. The roles of macrophages, autophagy and NETosis are also briefly discussed in the context of lung infections in COPD. Controlling their combined response…
Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells
2022
The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases.Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as “memory”.T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we exam…
Dacarbazine-mediated upregulation of NKG2D ligands on tumor cells activates NK and CD8 T cells and restrains melanoma growth.
2013
International audience; Dacarbazine (DTIC) is a cytotoxic drug widely used for melanoma treatment. However, the putative contribution of anticancer immune responses in the efficacy of DTIC has not been evaluated. By testing how DTIC affects host immune responses to cancer in a mouse model of melanoma, we unexpectedly found that both natural killer (NK) and CD8(+) T cells were indispensable for DTIC therapeutic effect. Although DTIC did not directly affect immune cells, it triggered the upregulation of NKG2D ligands on tumor cells, leading to NK cell activation and IFNγ secretion in mice and humans. NK cell-derived IFNγ subsequently favored upregulation of major histocompatibility complex cl…
Cutaneous Exposure to the Superantigen Staphylococcal Enterotoxin B Elicits a T-Cell-Dependent Inflammatory Response
1996
We analyzed the impact of superantigens secreted by skin-colonizing Staphylococci on the skin and the associated lymphoid tissue following epicutaneous application and intracutaneous injection of small amounts of staphylococcal enterotoxin B (SEB). A single intracutaneous injection of 50 ng of SEB elicited a strong inflammatory response in the skin of BALB/c mice. Three to 6 h later, we observed langerhans cell activation, mast cell degranulation, vasodilation, upregulation of ICAM-1, and induction of VCAM-1 on dermal blood vessels, with vascular adhesion of granulocytes. by 12 to 24 h, cell infiltration of the dermis increased, reaching the epidermis. Among the infiltrating leukocytes, a s…
Evidence against a key role for transforming growth factor-beta1 in cytomegalovirus-induced bone marrow aplasia.
1998
During immunodeficiency after sublethal haematoablative treatment, cytomegalovirus (CMV) infection interferes with haematopoietic reconstitution and can cause lethal bone marrow (BM) aplasia. The in vivo model of murine CMV infection has identified the BM stroma as the principal target site of CMV in the haematopoietic cord. The infected cell type is the reticular stromal cell which forms the stromal network and produces essential haemopoietins, such as stem-cell factor (SCF). The expression of SCF was found to be reduced in the infected stroma, but the stromal network was not disrupted and the number of infected stromal cells was too low to explain the functional deficiency. These facts ca…
Induction of tumor peptide-specific cytotoxic T cells under serum-free conditions by mature human dendritic cells
2000
Tumor vaccination strategies using antigen-pulsed dendritic cells (DC) are currently under development. We established an in vitro system using cultured DC from HLA-typed volunteers for the induction of tumor peptide-specific CD8+ T cells. The strength and specificity of the resulting CTL responses were investigated. For stimulation of syngeneic CD8+ T cells two well-defined DC populations were generated: CD1a+ immature DC cultured in the presence of GM-CSF and IL-4 and mature CD83+ DC generated by additional stimulation with a cytokine cocktail. Stimulations were performed under serum-free conditions and in the absence of exogenous cytokines. Analysis of T cell responses showed that mature…
Identification of HLA-A*0201-Restricted T Cell Epitopes Derived from the Novel Overexpressed Tumor Antigen Calcium-Activated Chloride Channel 2
2002
Abstract Vaccination against tumor Ags may become a promising treatment modality especially in cancer types where other therapeutic approaches fail. However, diversity of tumors requires that a multitude of Ags become available. Differential expression in normal vs cancerous tissues, both at the mRNA and the protein level, may identify Ag candidates. We have previously compared transcripts from squamous cell lung cancer and normal lung tissue using differential display analysis, and found a transcript that was overexpressed in malignant cells and was identical with the calcium-activated chloride channel 2 (CLCA2) gene. We have now selected HLA-A2-restricted peptides from CLCA2, and have gen…