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Biomedical subjects

M E Meijer-Paape

Publications and source records attributed to M E Meijer-Paape.

8 recordsLinked to original sources
PubMed1989

Donor-specific lysis of human kidney proximal tubular epithelial cells by renal allograft-infiltrating lymphocytes.

In the present study methods are described to obtain both graft infiltrating cells (GIC) of host origin and proximal tubular epithelial cells (PTEC) of donor origin simultaneously from biopsy material of renal allografts undergoing rejection. The identity of PTEC cultures was established using monoclonal antibodies. GIC were shown to exhibit T cell functional activity. These GIC were shown to lyse trypsinized PTEC as well as PTEC monolayers grown from the corresponding biopsy, and not PTEC isolated from biopsies obtained from other patients. Therefore the lytic activity appeared to be donor-specific. Major histocompatibility complex class I antigens were involved since donor PHA-blasts, a target population well known to express class I molecules, were lysed by GIC, and the anti-class I MoAb W6/32 blocked cytolytic activity of GIC against donor PHA-blasts and against donor PTEC. We thus established that donor-specific lysis of a defined population of kidney epithelial cells, namely PTEC, may occur. This model system, in which GIC and PTEC can be propagated from one biopsy specimen may be useful for further study of cell-cell interactions involved in allograft rejection.

Antibodies, Monoclonal↗
PubMed1989

Induction of antibody-dependent cellular cytotoxicity against endothelial cells by renal transplantation.

Antibodies that induce antibody-dependent cellular cytotoxicity (ADCC) of human umbilical-vein endothelial cells (EC) were detected using serum of a renal transplant patient who had experienced a severe vascular rejection episode after receiving an HLA-identical kidney graft from a living-related donor. This reactivity was absent in sera obtained before transplantation. The antibody nature of the reactivity present in the post-transplantation sera was proven by gelfiltration studies, protein A absorption, pepsin-digestion experiments, and incubation with subclass specific monoclonal antibodies; predominantly IgG1 antibodies were found to bind to EC and induce ADCC. The specificity of the antibodies could be shown in panel studies using EC lines of various donors. In order to investigate the clinical relevance and incidence of anti-EC ADCC, we examined whether anti-EC reactivity could be observed in 9 additional renal transplant patients. Sera of 2 of these patients were found positive in the ADCC assay, whereas 20 normal serum donors were negative. ADCC against EC in these patients was not caused by classic antiendothelial-monocyte (EM) antibodies. Using various experimental systems (adherent cell depletion, monoclonal antibody blocking, cold target cell inhibition) it was shown that the natural killer/killer (NK/K) cells present within the peripheral blood mononuclear cell population were responsible for EC lysis. These findings demonstrate that IgG1 antibodies directed against polymorphic non-HLA, non-EM antigens on EC can be induced by renal allotransplantation. Via Fc-receptor interaction with NK/K cells, these antibodies can be responsible for ADCC against EC.

Antibodies, Monoclonal↗
PubMed1988

Lymphokine-activated killer cells lyse human renal cancer cell lines and cultured normal kidney cells.

In this study, we investigated whether or not lymphokine-activated killer (LAK) cells can damage renal tissue and therefore whether they may contribute to graft destruction during kidney allograft rejection. Human peripheral blood mononuclear cells were activated with a lymphokine preparation and the resulting LAK cells were tested against kidney cells from various sources. Renal cancer cells as well as cultured normal kidney cells were efficiently lysed by LAK cells, as assessed with Cr-labelled target cells, showing that both cell types are sensitive to LAK cell-mediated cytolysis.

Cell Line↗
PubMed1988

Short-term lymphokine stimulation of human peripheral blood mononuclear cells generates cytolytic activity against endothelial cells: involvement of natural killer cells.

UNLABELLED: We previously reported that incubation of human peripheral blood mononuclear cells (PBMC) for 5 days with T-cell growth factor (TCGF) resulted in lymphokine-activated killer activity against endothelial cells (EC). In this paper we report on the effects of short-term incubation of PBMC with lymphokines. We show that incubation of PBMC with lymphokines during an 18-hr period is sufficient to generate a strong cytolytic response against EC. The cytolytic capacity of the effector cells was directly dependent on the dose of lymphokine added during the induction phase. When PBMC were separated into adherent and non-adherent cells, the non-adherent fraction could be induced to lytic activity against EC, whereas the adherent cells could not. When PBMC were separated, using 2-amino-ethylisothiouronium bromide hydrobromide-treated sheep red blood cells (AET-SRBC), into T- and non-T-cell fractions, the latter fraction could be induced to lyse EC. TCGF-induced cell-mediated EC lysis could not be inhibited using anti-T3 nor anti-LFA-1 antibodies. Lysis of EC by TCGF-stimulated effector cells was strongly inhibited by the addition of unlabelled K562 target cells, whereas cold OKT3 hybridoma cells did not exert such an effect. IN CONCLUSION: the kinetics of the induction of lytic activity against EC, as well as the cell separation experiments, suggest that short-term-activated NK cells may lyse EC. This hypothesis was confirmed using monoclonal antibody and cold target cell analysis.

Cell Adhesion↗
PubMed1987

Endothelial cell lysis induced by lymphokine-activated human peripheral blood mononuclear cells.

In vitro exposure of human peripheral blood mononuclear cells (PBMC) to interleukin 2 results in the generation of lymphokine-activated killer (LAK) cells. Such LAK cells exhibit cytotoxicity against a spectrum of tumor target cell lines whereas they apparently do not affect normal tissues. In this report we show that PBMC that have been activated with T cell growth factor lyse trypsinized human umbilical cord venous endothelial cells as well as endothelial cell monolayers in a dose-dependent manner. Microscopic analysis showed that during the 4-h incubation period cell clumps containing detached endothelial cells and LAK cells were formed. When these clumps were evaluated with trypan blue the endothelial cells stained positive whereas LAK cells excluded the dye. No lysis occurred when fresh PBMC were added to target endothelial cells. The endothelial cell kill could not be blocked with an anti-LFA-1 antibody nor with intact OKT3 or F(ab')2 fragments of WT32. We conclude that lymphokine-activated PBMC exhibit cell-mediated endothelial cell detachment and lysis.

Antibodies, Monoclonal↗
PubMed1987

Inhibition of T cell cytolytic potential by concanavalin A: a result of activation?

We investigated the effects of concanavalin A (Con A) on T cell-mediated lympholysis. Human cytotoxic T cell lines were generated from peripheral blood and these lines were shown to lyse lectin-coated K562 target cells. Addition of soluble Con A to the assay resulted in a dose-dependent inhibition of the cytolysis. Preincubation experiments demonstrated that this inhibitory effect was exerted at the effector cell level. F(ab')2 fragments of WT32, a monoclonal antibody against T3, blocked the cytolysis of Con A-preincubated K562 target cells to a large extent. We further showed that Con A strongly inhibited the cytolysis exerted by alloantigen-specific, major histocompatibility complex (MHC)-restricted cytotoxic T cell lines against their specific targets. On the other hand, Con A had no clear inhibitory effect on the cytotoxicity of freshly isolated peripheral blood mononuclear cells against K562 target cells. We hypothesize that Con A-induced inhibition of cytotoxicity may be explained by a direct triggering of the lytic potential of activated T cells.

Antigens, Differentiation, T-Lymphocyte↗