Search results for "T-Cell"
showing 10 items of 458 documents
ILCs and T Cells Competing for Space: More Than a Numbers Game.
2017
T cell homeostasis critically depends on interleukin-7 (IL-7). In this issue of Immunity, Martin et al. (2017) provide evidence that IL-7 availability is regulated through a "cytokine sink" involving innate lymphoid cells that compete for and consume IL-7 and thereby restrict T cell homeostasis in lymphoid organs.
Generation of TCR-engineered reference cell samples to control T-cell assay performance
2020
In vitro cellular assays analyzing antigen-specific T cells are characterized by their high complexity and require controlled conditions to lower experimental variations. Without standard cellular reagents, it is difficult to compare results over time and across institutions. To overcome this problem, a simple and robust technology was developed to generate TCR-engineered reference samples (TERS) containing defined numbers of antigen-specific T cells. Utilization of TERS enables performance control of three main T-cell assays: MHC-peptide multimer staining, IFN-gamma ELISpot and cytokine flow cytometry. TERS continuously deliver stable results and can be stored for longer periods of time. H…
Nitensidine A, a guanidine alkaloid from Pterogyne nitens, is a novel substrate for human ABC transporter ABCB1.
2014
The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to produce guanidine alkaloids as well as bioactive flavonols such as kaempferol, quercetin, and rutin. In the present study, we examined the possibility of interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four guanidine alkaloids isolated from P. nitens (i.e., galegine, nitensidine A, pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared to CCRF-CEM cells, although the four guanidine alkaloids exhibi…
Targeting Acute Leukemia and Cancer by High-Affinity T-Cell-Receptor Transfer
2003
Accumulation and subsequent overexpression of human mdm2 (hdm2) and altered p53 protein is associated with high-level presentation of hdm2 and wild-type (wt) p53 derived peptides by major histocompatibility complex (MHC) class I molecules on a wide range of malignant cells. A major barrier to the design of broad-spectrum hdm2 and p53 specific immunotherapeutics for leukemia and cancer, however, has been the observation that low-level expression of hdm2 and wt p53 peptides by non-transformed tissues and cells results in self-tolerance of T-lymphocytes with high avidity for self-class I MHC / self-peptide complexes. Although the peripheral T-cell repertoire is mostly devoid of such high-avidi…
CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death
2011
Abstract Extracellular adenosine (ADO), generated from ATP or ADP through the concerted action of the ectoenzymes CD39 and CD73, elicits autocrine and paracrine effects mediated by type 1 purinergic receptors. We have tested whether the expression of CD39 and CD73 by chronic lymphocytic leukemia (CLL) cells activates an adenosinergic axis affecting growth and survival. By immunohistochemistry, CD39 is widely expressed in CLL lymph nodes, whereas CD73 is restricted to proliferation centers. CD73 expression is highest on Ki-67+ CLL cells, adjacent to T lymphocytes, and is further localized to perivascular areas. CD39+/CD73+ CLL cells generate ADO from ADP in a time- and concentration-dependen…
Aminobisphosphonates as new weapons for gammadelta T Cell-based immunotherapy of cancer.
2008
BACKGROUND: Activated V gamma 9 V delta 2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors. OBJECTIVE: We discuss the possibility that the intentional activation of gammadelta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients. METHODS: The antitumoral effects of gammadelta T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting. RESULTS/CONCLUSION: V gamma 9 V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic …
Gene Therapy With a High-Affinity Single-Chain p53-Specific TCR Mediates Potent Anti-Tumor Response Without Inducing Gvhd In Vivo
2013
Abstract The adoptive transfer of tumor-reactive cells is a promising approach in the treatment of human malignancies, but the challenge of isolating T cells with high-avidity for tumor antigens in each patient has limited its widespread application. Using HLA-A2.1 transgenic mice, we have demonstrated the feasibility of T-cell receptor (TCR) gene transfer into T cells to circumvent self-tolerance to the widely expressed human p53(264-272) tumor-associated antigen and developed approaches to generate high-affinity CD8-independent TCR. However, a safety concern of TCR gene transfer is the risk of pairing between introduced and the naturally expressed endogenous TCR chains, resulting in the g…
Increasing Functional Avidity of T Cell Receptor (TCR)-Redirected T Cells by Removing Defined N-Glycoslyation Sites in the Constant Domain of Introdu…
2007
Abstract Adoptive transfer of T lymphocytes transduced with a TCR to impart tumor reactivity has been reported as potential strategy to redirect immune responses to target cancer cells. However, the affinities of most TCRs specific for shared tumor antigens that can be isolated are usually low, in part reflecting the nature of the targeted tumor antigens which are self-proteins. Thus strategies that can increase the affinity or functional avidity of TCRs to be used in therapy to transduce T cells might be therapeutically beneficial. However, current strategies for increasing TCR affinity require extensive and usually random mutagenesis followed by screening the many derived mutations, and m…
Genetic proof for the transient nature of the Th17 phenotype
2010
IL-17-producing CD4(+) T cells (Th17) have been classified as a new T helper cell subset. Using an IL-17 fate mapping mouse strain, which genetically fixes the memory of IL-17 expression, we demonstrate that IL-17A/F-expressing T helper cells generated either in vitro or in vivo are not a stable T-cell subset. Upon adoptive transfer of IL-17F-reporter-positive Th17 cells to RAG-deficient or WT animals, encephalitogenic Th17 cells partially lose IL-17 expression and upregulate IFN-γ. Additionally, we show that Th1 cells can convert in vivo to IL-17A/IFN-γ-coexpressing cells in the mesenteric lymph nodes (mLN). Our data classify IL-17A and IL-17F as cytokines produced transiently in response …
T cells expressing a chimeric antigen receptor that binds hepatitis B virus envelope proteins control virus replication in mice.
2013
Background & Aims Antiviral agents suppress hepatitis B virus (HBV) replication but do not clear the infection. A strong effector T-cell response is required to eradicate HBV, but this does not occur in patients with chronic infection. T cells might be directed toward virus-infected cells by expressing HBV-specific receptors and thereby clear HBV and help to prevent development of liver cancer. In mice, we studied whether redirected T cells can engraft after adoptive transfer, without prior T-cell depletion, and whether the large amounts of circulating viral antigens inactivate the transferred T cells or lead to uncontrolled immune-mediated damage. Methods CD8 + T cells were isolated from m…