Search results for "Cytotoxic"
showing 10 items of 1673 documents
Secondary cytotoxic allograft responsein vitro. I. Antigenic requirements
1975
The antigenic requirementsfor in vitro induction of secondary murine cytotoxic allograft responses were tested. The proliferative responses were assayed by the [3H]thymidine uptake technique; the generation of cytotoxic T lymphocytes (CTL) was tested in a 51Cr-cytotoxicity assay. Spleen cells from normal or alloantigen preimmunized CBA mice (H-2k) were used as responder cells. Allogeneic x-irradiated splenic lymphocytes (normal stimulator cells) were UV light treated, heat treated or glutaradehyde fixed and subsequently tested for their capacity to induce CTL in a primary or secondary mixed lymphocyte culture (MLC). In addition allogeneic fibroblasts were tested as stimulator cells. The res…
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…
Defective expression of CD95 (FAS/APO-1) molecule suggests apoptosis impairment of T and B cells in HLA-B8, DR3-positive individuals.
1997
Activation-induced apoptosis is one of the primary control mechanisms for the negative selection of an immune response, leading to maintenance of immune homeostasis and selective T cell deletion. The interaction between the surface molecule Fas and its ligand (FasL) has been proposed as a primary mechanism initiating T cell apoptosis. The T cell receptor modulates the expression and function of these molecules. Defects in the Fas/FasL apoptosis pathway have been shown to result in autoimmune disease in humans and in murine models. Because subjects carrying the HLA-B8, DR3 haplotype show a number of immune dysfunctions, including membrano-proliferative glomerulonephritis, systemic lupus eryt…
Antigen-independent in vitro expansion of T cells does not affect the T cell receptor V beta repertoire.
1997
Analysis of the variable chains (V alpha/V beta) of the specific T cell receptor (TCR) of organ-infiltrating T cells may provide further insights into the pathogenesis of many infectious diseases, malignancies, and autoimmune disorders. To determine the TCR V beta repertoire of these small T cell populations antigen-independent in vitro expansion is necessary but may select for certain T cell subpopulations. In this study various antigen independent T cell activation protocols were used to stimulate peripheral blood mononuclear cells (PBMC) of six healthy blood donors, and TCR V beta molecules were analyzed by flow cytometry and semiquantitative reverse-transcriptase polymerase chain reacti…
Anti-GD3 antibodies are potent activators of human gamma/delta and alpha/beta positive T cells.
1995
The ganglioside GD3 has a variety of biological functions. These include stimulatory effects on proliferation, natural killer activity and cytokine production by freshly isolated peripheral T cells. In this study we have characterized anti-GD3 antibody (MoAb Z21) mediated effects on T cell clones. Our data indicate that alpha/beta TCR CD4+ and CD8+ as well as gamma/delta TCR positive T cells can be stimulated resulting in proliferation and cytokine production. This effect could be blocked by cyclosporin A and did not involve the LFA-3 or CD4 molecule. Apart from IFN-gamma and IL-2 production by T helper 1 and T helper 0 cells we have observed production of IL-4 and IL-10 by T helper 2 cells…
LFA-1 Contributes to Signal I of T-Cell Activation and to the Production of Th1 Cytokines
2010
The beta(2) integrins are important for both transendothelial migration of leukocytes and T-cell activation during antigen presentation. In T cells, triggering of leukocyte functional antigen-1 (LFA-1) is required for full activation and T-helper (Th)1/Th2 differentiation. We used CD18-deficient (CD18(-/-)) mice to examine the role of LFA-1 in the activation of T cells. Compared with wild-type controls, CD18(-/-) T cells proliferated normally when stimulated with antibodies against CD3 and CD28, but secreted significantly less IFN-gamma and IL-2 than their wild-type counterparts. However, when T cells were stimulated with dendritic cells (DCs) that provide additional LFA-1 ligation, the pro…
Specific Targeting of Cytokine-Secreting Cells: A Bispecific Diabody Recognizing Human Interleukin-6 and CD3 Induces T Cell-Mediated Killing
1998
Cytokines have been implicated in the pathophysiology of many diseases. Although there have been many attempts to neutralize the activity of cytokines in vivo and in vitro, no strategies have been developed to specifically eliminate cells that overexpress cytokines. Considering the fact that cytokines in part remain cell associated on secretion, we have constructed a bispecific diabody consisting of a nonneutralizing scFv antibody recognizing human interleukin-6 (IL-6) and an scFv corresponding to the monoclonal antibody (mAb) OKT3, which recognizes and activates the human T cell receptor. Here we show that the diabody recognized both human IL-6 and human CD3. In the presence of human T cel…
In Vitro Expansion of Human Tumor-Reactive CD8+ T Cell Lines Using Superparamagnetic CD3/CD28/CD137 Beads.
2009
Abstract Abstract 5118 Introduction Efficient methods for the reliable in vitro expansion of tumor-reactive T cells will surely broaden the applicability of adoptive T cell therapy in cancer. In this study we investigated the antigen-independent stimulation and expansion of human T cells in peripheral blood mononuclear cells (PBMC) and in long-term cultured tumor-reactive CD8+ T cell lines using superparamagnetic beads coated with antibodies to CD3 and the costimulatory molecules CD28 and CD137. Methods T cell numbers were measured in healthy donor PBMC after in vitro stimulation with Dynabeads® coated with CD3/CD28/CD137 versus Dynabeads® coated with CD3/CD28 (all beads +/- 100 U/mL IL-2) …
Activation of phenotypically heterogeneous murine T cell receptor gamma delta + dendritic epidermal T cells by self-antigen(s).
1995
Adult murine epidermis contains a population of Thy-1+, CD45+, CD3+, CD4- and CD8- in situ primarily T cell receptor (TCR) V gamma 3+/V delta 1+ dendritic epidermal T cells (DETC). In the present study, cell surface phenotypes as well as functional properties of DETC were characterized by using in vitro mitogen-stimulated short-term- (10 days) and cloned long-term-cultured (1 year) DETC lines. Phenotypic characterization revealed that80% of the short-term-cultured cells were routinely TCR gamma delta +, CD4-, CD8-. The majority expressed the V gamma 3 TCR. Seventy-five percent of the lines contained detectable numbers of V gamma 2+ (5-7%) and V gamma 2-3- cells (2-3%). Four different types …
Delivering all in one: Antigen-nanocapsule loaded with dual adjuvant yields superadditive effects by DC-directed T cell stimulation
2018
Therapeutic vaccination is and remains a major challenge, particularly in cancer treatment. In this process, the effective activation of dendritic cells by a combination of distinctly acting adjuvants and an antigen is crucial for success. While most common vaccine formulations lack the efficiency to trigger sufficient T cell responses in a therapeutic tumor treatment, nanovaccines offer unique properties to tackle that challenge. Here, we report the stepwise development of a nanocapsule for vaccination approaches, comprising a shell consisting of antigen and loaded with a superadditive adjuvant combination. In a first initial step, we identified the combination of resiquimod (R848) and mur…