Search results for "Toxicity tests"
showing 10 items of 141 documents
Partial and Ineffective Activation of Vγ9Vδ2 T Cells by Mycobacterium tuberculosis-Infected Dendritic Cells
2010
Abstract γδ T cells and dendritic cells (DCs) participate in early phases of immune response against Mycobacterium tuberculosis. We investigated whether a close functional relationship exists between these two cell populations using an in vitro coculture in a human system. Vγ9Vδ2 T cells induce full maturation of M. tuberculosis-infected immature DCs, as demonstrated by upregulation of the costimulatory CD80, CD86, CD40, and HLA-DR molecules on infected DCs after 24 h of coculture. Reciprocally, infected DCs induced substantial activation of Vγ9Vδ2 T cells upon coculture, which was cell-to-cell contact and TCR dependent, as demonstrated in transwell experiments. However, infected DCs select…
Natural killer and lymphokine-activated killer activity in HLA-B8,DR3-positive subjects.
1993
Abstract The haplotype HLA-B8,DR3 is over-represented in several autoimmune diseases, implying that genes predisposing people to these disorders are linked to this haplotype. In these diseases, various dysfunctions reflecting an impairment of the immune system have been found. Several reports indicate also that in HLA-B8,DR3-positive healthy subjects similar disorders may be demonstrated. In the present work, we have evaluated NK and LAK activity in these subjects. The study has been performed on monocyte-depleted peripheral blood MNCs by using the K-562 cell line as a target for NK activity and the HL-60 cell line for as a target LAK activity. LAK cells were obtained by incubating MNCs for…
Toxicity assessment and biodegradation potential of water-soluble sludge containing 2,4,6-trinitrotoluen
2013
The water-soluble phase of trinitrotoluene-containing sludge (SLP) was characterized with regard to trinitrotoluene (TNT) concentration, ecotoxicity, and a model biodegradation experiment as evaluation criteria for further development of appropriate treatment technologies. SLP contained 67.8 mg TNT/l. The results of germination and root-elongation tests indicated that SLP had a species-specific phytotoxic effect. The results of a 21 day degradation experiment demonstrated TNT conversion to 4-amino-2,6-DNT and 2-amino-4,6-DNT, with a simultaneous reduction in the total concentration of nitroaromatics. Addition of inoculum stimulated the TNT degradation process. The presence of the sludge sol…
Enzymatic Activity of CD26 (Dipeptidylpeptidase IV) is not Required for Its Signalling Function in T Cells
1993
Abstract CD26 is a proteolytic enzyme (dipeptidylpeptidase IV) expressed on the T cell surface that defines an alternative activation signal for human T lymphocytes. Crosslinking of CD26 via monoclonal antibodies triggers proliferation and cytotoxicity in preactivated T cells. In this study, we used highly specific competitive and irreversible inhibitors of dipeptidylpeptidase IV to study the role of the enzymatic activity in activation of CD26- transfected T cells as well as of CD26-expressing normal human T cell clones. These inhibitors at concentrations that blocked up to 95% of the enzymatic activity, did not specifically inhibit T cell activation neither via TCR/CD3 nor via CD26 itself…
Safer chemicals using less animals: kick-off of the European ONTOX project
2021
The 3Rs concept, calling for replacement, reduction and refinement of animal experimentation, is receiving increasing attention around the world, and has found its way to legislation, in particular in the European Union. This is aligned by continuing high-level efforts of the European Commission to support development and implementation of 3Rs methods. In this respect, the European project called "ONTOX: ontology-driven and artificial intelligence-based repeated dose toxicity testing of chemicals for next generation risk assessment" was recently initiated with the goal to provide a functional and sustainable solution for advancing human risk assessment of chemicals without the use of animal…
Generation of chemotactic activity by immune complexes carrying clustered or nonclustered C&42horbar; sites
1973
Sensitized cells (EA) bearing different numbers of &42horbar; sites were tested for their ability to generate chemotactic activity from C-EDTA. From the results it can be shown that: 1 the amount of chemotactic activity generated parallels the number of &42horbar; sites bound to the cell surface, 2 all &42horbar; sites clustered around a single hemolytic site are enzymatically active as far as generation of chemotactic activity is concerned, and, 3 no difference can be demonstrated with IgG or IgM antibodies
Differences in non-MHC restricted cytotoxic activities of human peripheral blood lymphocytes after transfusion with allogeneic leukocytes or platelet…
1990
Abstract MHC-unrestricted cytotoxic activity of peripheral blood lymphocytes (PBL) from 4–6 healthy donors was investigated before and after transfusion with allogeneic leukocytes or platelets. Natural killer and lectin-dependent cellular cytotoxicity (LDCC) of PBL was tested against K562 and Raji target cells in a 4-h and 16-h 51 Cr-release assay, respectively. After allotransfusion with leukocytes, we found increased cytotoxic activity of each donor's PBL against all the three targets on day 3 or 7. The highest non-specific cytotoxic activity was detected against the relatively NK resistant Raji target cells. The increase of cytotoxic activity was lowest against the LDCC target (PHA-treat…
T cell-mediated cytotoxicity: discrimination between antigen recognition, lethal hit and cytolysis phase.
1974
Using a 51Cr release cytotoxicity assay, the cytotoxic effector phase of in vitro activated mouse T lymphocytes (killer cells) against 51Cr-labeled target cells has been investigated. It is shown that within 5–10 minutes of contact between killer cells and target cells, the target cells are already committed to lysis, therefore, antigen recognition and “lethal hit” must have taken place within this period of time. In contrast, target cell lysis (cytolysis phase) requires up to 3–4 h in order to be completed; it occurs independently of killer cells and it is highly temperature dependent. The killer cell-dependent phase (antigen-recognition and “lethal hit”) is dissociated into two consecutiv…
Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines.
2006
AbstractIn HLA-incompatible hematopoietic stem cell transplantation, alloreactive donor T cells recognizing recipient mismatch HLA cause severe graft-versus-host disease (GVHD). Strategies allowing the selective depletion of alloreactive T cells as well as the enhancement of graft-versus-malignancy immunity would be beneficial. We generated donor CD8 T-cell lines in vitro using allogeneic recipient cells mismatched at a single HLA class I allele or haplotype as stimulators. Recipient cells were obtained from acute myeloid leukemias, renal-cell carcinomas, and CD40L-induced B lymphoblasts. Resulting alloreactive T cells were activated by incubating day 21 T-cell cultures with HLA-mismatch tr…
Allorestricted T lymphocytes with a high avidity T-cell receptor towards NY-ESO-1 have potent anti-tumor activity.
2009
The cancer-testis antigen NY-ESO-1 has been targeted as a tumor-associated antigen by immunotherapeutical strategies, such as cancer vaccines. The prerequisite for a T-cell-based therapy is the induction of T cells capable of recognizing the NY-ESO-1-expressing tumor cells. In this study, we generated human T lymphocytes directed against the immunodominant NY-ESO-1(157-165) epitope known to be naturally presented with HLA-A*0201. We succeeded to isolate autorestricted and allorestricted T lymphocytes with low, intermediate or high avidity TCRs against the NY-ESO-1 peptide. The avidity of the established CTL populations correlated with their capacity of lysing HLA-A2-positive, NY-ESO-1-expre…