Search results for "Phenotyping"
showing 10 items of 197 documents
Interferon-α Abrogates Tolerance Induction by Human Tolerogenic Dendritic Cells
2011
Background Administration of interferon-α (IFN-α) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance induction by human tolerogenic dendritic cells (DC) was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC) that are known to induce anergic regulatory T cells (iTregs). Methodology/Principal Findings IFN-α promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-α treatment resulted in an…
T-Cell Subsets (TCM, TEM, TEMRA) and Poly-Functional Immune Response in Patients with Human Immunodeficiency Virus (HIV) Infection and Different T-CD…
2019
OBJECTIVE: Dynamic changes of cytotoxic T cell responses against Human Immunodeficiency Virus 1 (HIV-1) infection have been the subject of an innovative investigation using antiretroviral therapy (ART). Currently, human CD8 naïve central memory (TCM), effector memory (TEM), and effector memory cells re-expressing CD45RA (TEMRA) T-cells have been thoroughly studied with ART. CD45RA is a marker usually found on naïve T-cells. MATERIALS AND METHODS: We performed a longitudinal study of mono-/polyfunctional T-cells in the peripheral blood while targeting three functionally distinct cell populations of CD4+ and CD8+ T-cells (single IL2 and IFN-γ, dual IL2/IFN-γ) in 50 HIV-1 patients. These patie…
Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production
2003
Abstract Background: Recently, it has been established that CD4 + CD25 + T cells with regulatory capacity are present in human peripheral blood, inhibiting allogeneic proliferation and cytokine production of preactivated CD4 + CD25 − respond-er T cells. Objective: The aim of this study was to analyze in an allergen-specific setting whether such regulatory CD4 + CD25 + T cells also exist and function normally in atopic individuals, especially concerning the inhibition of T H 2 cytokines. Methods: For this purpose, CD4 + CD25 − or CD4 + CD25 + T cells from donors allergic to grass or birch pollen (mainly with rhinitis) or from healthy nonatopic donors were stimulated in the presence of autolo…
Gene Therapy of Human Melanoma — from Animal Experiments to the Clinical Trial
1997
Low immunogenecity of tumour cells is one of the reason that specific immune response is insufficient to destroy malignant cells. In an attempt to augment weakly immunogenic B78H1 mouse melanoma cell line, these cells were transfected with genomic DNA from a line of human melanoma cells expressing a 96kD melanoma associated antigen (MAA) that is intercellular adhesion molecule 1 (ICAM 1). The transfected cells expressed fivefold higher quantities of the melanoma associated antigen from which the DNA was obtained. Human ICAM 1 expressed by mouse melanoma cells appeared to be highly immunogenic leading to the rejection of the modified mouse melanoma cells. The transfected cells appeared to be…
An anti-inflammatory role for V alpha 14 NK T cells in Mycobacterium bovis bacillus Calmette-Guérin-infected mice.
2003
Abstract The possible contribution of NKT cells to resistance to Mycobacterium tuberculosis infection remains unclear. In this paper we characterized the Vα14 NKT cell population following infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG). BCG infection determined an early expansion of Vα14 NKT cells in liver, lungs, and spleen, which peaked on day 8 and was sustained until day 30. However, an NK1.1+ Vα14 NKT population preferentially producing IFN-γ predominated at an early stage (day 8), which was substituted by an NK1.1− population preferentially producing IL-4 at later stages (day 30). Despite the fact that Vα14 NKT cell-deficient mice eliminated BCG as did control mice…
Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody
2008
Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non–Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell–engag…
The Late Endosomal Adaptor Molecule p14 (LAMTOR2) Regulates TGFβ1-Mediated Homeostasis of Langerhans Cells
2014
Langerhans cells (LCs), a sub-population of dendritic cells (DCs) in the skin, participate in the regulation of immunity and peripheral tolerance. The adaptor molecule p14 is part of the late endosomal/lysosomal adaptor and mitogen-activated protein kinase and mammalian target of rapamycin (mTOR) activator/regulator (LAMTOR) complex, which mediates the activation of lysosome-associated extracellular signaling regulated kinase (ERK) and the mTOR cascade. In previous work, we demonstrated that CD11c-specific deficiency of p14 disrupts LC homeostasis by affecting the LAMTOR-mediated ERK and mTOR signaling. In this study, we extended our analysis on p14 deficiency specifically in LCs. Langerin-…
Phenotypic characterisation of pro-inflammatory monocytes and dendritic cells in peripheral arterial disease
2012
SummaryAtherosclerosis is a chronic inflammatory process involving antigen-presenting cells like monocytes and dendritic cells (DC). The aim of this study was to perform a phenotypic characterisation of these cell types in patients with different degrees of peripheral arterial disease (PAD). Sixty patients with PAD [N= 30 intermittent claudication (IC), N= 30 critical limb ischemia (CLI)] and 30 controls were included. Peripheral blood leucocytes were analysed from peripheral blood by flow cytometry using different gating strategies to directly identify and analyse monocytes, myeloid DC, (mDC) and plasmacytoid DC (pDC). PAD patients showed a significantly higher proportion of proinflammator…
Deletion of 11q in Neuroblastomas Drives Sensitivity to PARP Inhibition
2017
AbstractPurpose: Despite advances in multimodal therapy, neuroblastomas with hemizygous deletion in chromosome 11q (20%–30%) undergo consecutive recurrences with poor outcome. We hypothesized that patients with 11q-loss may share a druggable molecular target(s) that can be exploited for a precision medicine strategy to improve treatment outcome.Experimental Design: SNP arrays were combined with next-generation sequencing (NGS) to precisely define the deleted region in 17 primary 11q-loss neuroblastomas and identify allelic variants in genes relevant for neuroblastoma etiology. We assessed PARP inhibitor olaparib in combination with other chemotherapy medications using both in vitro and in v…
Differential impact of high and low penetrance TNFRSF1A gene mutations on conventional and regulatory CD4+ T cell functions in TNFR1-associated perio…
2015
Abstract TNFR-associated periodic syndrome is an autoinflammatory disorder caused by autosomal-dominant mutations in TNFRSF1A, the gene encoding for TNFR superfamily 1A. The lack of knowledge in the field of TNFR-associated periodic syndrome biology is clear, particularly in the context of control of immune self-tolerance. We investigated how TNF-α/TNFR superfamily 1A signaling can affect T cell biology, focusing on conventional CD4+CD25− and regulatory CD4+CD25+ T cell functions in patients with TNFR-associated periodic syndrome carrying either high or low penetrance TNFRSF1A mutations. Specifically, we observed that in high penetrance TNFR-associated periodic syndrome, at the molecular le…