Search results for "Immune system"
showing 10 items of 2885 documents
The immunodominant CD8 T cell response to the human cytomegalovirus tegument phosphoprotein pp65(495-503) epitope critically depends on CD4 T cell he…
2011
Abstract Immunodominance hierarchies operating in immune responses to viral Ags limit the diversity of the elicited CD8 T cell responses. We evaluated in I-Ab+/A2-HHD-II and HLA-DR1+/A2-DR1 mice the HLA-A*0201–restricted, multispecific CD8 T cell responses to the human CMV tegument phosphoprotein pp65 (pp65) Ag. Vaccination of mice with pp65-encoding DNA elicited high IFN-γ+ CD8 T cell frequencies to the pp65495–503/(e6) epitope and low responses to the pp65320–328/(e3) and pp65522–530/(e8) epitopes. Abrogation of the e6-specific immunity efficiently enhanced e3- and e8-specific T cell responses by a pp65Δ501–503 DNA vaccine. The immunodominant e6-specific (but not the e3- and e8-specific) …
A CD40/CD40L feedback loop drives the breakdown of CD8+T-cell tolerance following depletion of suppressive CD4+T cells
2014
Dendritic cells (DCs) are the key APCs not only for the priming of naive T cells, but also for the induction and maintenance of peripheral T-cell tolerance. We have recently shown that cognate interactions between Foxp3(+) Tregs and steady-state DCs are crucial to maintain the tolerogenic potential of DCs. Using DIETER mice, which allow the induction of antigen presentation selectively on DCs without altering their maturation status, we show here that breakdown of CD8(+) T-cell tolerance, which ensues after depletion of suppressive CD4(+) T cells, is driven by a positive feedback loop in which autoreactive CD8(+) T cells activate DCs via CD40. These data identify ligation of CD40 on DCs as …
Quantitative representation of all T cells committed to develop into cytotoxic effector cells and/or interleukin 2 activity-producing helper cells wi…
1984
A limiting dilution culture system based on stimulation with concanavalin A (Con A) has been used to study the quantitative distribution of helper and of cytotoxic precursor cells in Lyt-2-defined subpopulations of murine T cells. Virtually all of the selected Lyt-2+ and Lyt-2-T cells grow and expand to large clonal colonies within an 8-9-day culture period. Our data show that upon stimulation with Con A, 90% of the Lyt-2-T cells were capable to produce interleukin 2 (IL 2) activity. In addition, IL 2 activity is produced by 8-10% of Lyt-2+ T cells. However, at the clonal level, the average of the IL2 activity produced by Lyt-2+ T cells is about 8-fold less as compared to Lyt-2-T cells. Pre…
A rapid and simple multiparameter assay to quantify spike-specific CD4 and CD8 T cells after SARS-CoV-2 vaccination: A preliminary report
2021
mRNA and Adenovirus vaccines for COVID-19 are used to induce humoral and cell-mediated immunity, with the aim to generate both SARS-CoV-2 B and T memory cells. In present study, we described a simple assay to detect and quantify Spike-specific CD4+ and CD8+ T cell responses induced by vaccination in healthy donors and in subjects with B cell compart impairment, in which antibody response is absent due to primary immunodeficiencies or CD20 depleting therapy. We detect and quantified memory T cell immune responses against SARS-CoV-2 evocated by vaccination in both groups, irrespective to the humoral response. Furthermore, we identified TNF-α as the main cytokine produced by T memory cells, af…
Functionally Altered GPI-Anchor Negative Treg Following Alemtuzumab-Based T-Cell Depletion Are Associated with Acute Gvhd.
2012
Abstract Abstract 3059 Introduction: The monoclonal anti-CD52antibody Alemtuzumab is frequently used for T-cell depletion (TCD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT) to prevent graft versus host disease (GVHD). We previously demonstrated the long term persistence of functionally impaired glycosylphosphatidylinositol (GPI)-anchor negative effector T-cells in patients receiving high dose (100mg) Alemtuzumab in combination with a dose reduced conditioning regimen (Fludarabin + Melpahlan) (Meyer, Wagner et al. BMT 2010). Despite of Alemtuzumab-mediated TCD, half of our patients developed acute GVHD. Since regulatory T cells (Treg) play a major role for cont…
CD40 signalling induces IL-10-producing, tolerogenic dendritic cells
2010
Dendritic cells (DC) are potent antigen-presenting cells capable to induce efficient antigen-specific T cell responses in vitro and in vivo. Herein, the maturation process is of great significance, as immature DC (iDC) are known to induce rather regulatory than effector T cell differentiation. This study was designed to characterize the role of the CD40-CD40L pathway for differentiation and function of human DC. Therefore, iDC were stimulated through CD40-CD40L interaction by transduction of DC with adenoviral vectors encoding for CD40L (Ad-CD40L). Resulting DC (CD40L-DC) were analysed concerning their phenotype, cytokine profile and T cell stimulatory capacity. Transduction induced a DC ph…
ICOS and CD28 reversely regulate IL-10 on re-activation of human effector T cells with mature dendritic cells
2002
With newly generated ICOS-ligand (ICOS-L)-specific monoclonal antibodies we determined that human Langerhans cells in situ express similar levels of ICOS-L, CD80, and CD86, compared to immature dendritic cells (DC) derived from monocytes in vitro. Maturation of DC strongly up-regulated CD80 and CD86 but did not significantly change ICOS-L levels. On coculture of "naive"CD4(+) T cells with mature DC in the presence of superantigen, ICOS was highly up-regulated on T cells, but played only a secondary role in the CD28-dominated release of TNF-alpha and IFN-gamma, and did not participate in the induction of IL-2. Cocultures of "effector" CD4(+) T cells with mature DC revealed CD28 as the drivin…
Differences in Dendritic Cell Activation and Distribution After Intravenous, Intraperitoneal, and Subcutaneous Injection of Lymphoma Cells in Mice
2007
Dendritic cells (DCs) are key antigen-presenting cells (APCs) for initiating immune responses. However, in recent years, several groups have shown the defective function of DCs in tumor-bearing mice and in cancer patients. Our aim was to study the effects of lymphoma on DC differentiation and maturation and to assess the input of the tumor microenvironment and intravasation of tumor cells on DC precursors. EL-4 lymphoma cells were administrated via different routes (intraperitoneal, subcutaneous, and intravenous) and DC phenotype was investigated. Bone marrow-derived DCs and APCs obtained from the spleen were examined by flow cytometry, and immunohistochemical analysis of lymphoma, lungs, l…
TLR4 and NOD1 increase in stable COPD of increasing severity. Relationship with tissutal bacterial load
2016
Background: The immune host response related to bacterial and viral infections in the airways and lung of COPD patients is unclear. Objectives: To investigate the expression of anti-bacterial and anti-viral antigens in bronchial biopsies and lung parenchyma of stable COPD patients in relation to bacterial load. Methods: Immunohistochemical (IHC) and qRT-PCR-expression of TLR2-3-4-7-8-9, NOD1, NOD2, MYD88, TRIF, TIRAP, pIRAK1, IRAK4, IRF3, pIRF3, IRF7, pIRF7, RIG1, MDA5, LGP2, MAVS, STING, DAI, IFNα and IFNβ was measured in bronchial mucosa in patients with mild/moderate (n=16), severe/very severe (n=18) stable COPD, control smokers (n=12) and control non-smokers (n=12). Selected relevant an…
PHEA-graft-polymethacrylate supramolecular aggregates for protein oral delivery
2013
Abstract Salmon calcitonin (sCT) is characterized by a poor oral availability. A new copolymer, β-poly(N-2-hydroxyethyl)-graft-{N-2-ethylene[2-poly(methacrylic acid sodium salt)isobutyrate]}- d , l -aspartamide (PHEA-IB-p(MANa + )), was designed for the oral administration of sCT through the formation of supramolecular aggregates (SAs) based on electrostatic interactions. Several sCT/PHEA-IB-p(MANa + ) weight ratios were characterized by turbidimetry, DLS, zeta potential, and microscopy analysis. After the incubation of sCT/PHEA-IB-p(MANa + ) complex with digestive enzymes, 10% (w/w) of loaded sCT was released in the native form. In vitro investigation was carried out to determine the copol…