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V Toder

Publications and source records attributed to V Toder.

At least 91 records · Page 5Linked to original sources

Studies of natural killer cells in pregnancy. I. Analysis at the single cell level.

In using both a 51Cr-release assay and a single cell technique we measured different parameters of the effector lymphocytes killing process in pregnant and control women on a cell population and single cell level. Total NK activity was lower in pregnancy, but the difference was not significant. Parity showed no cumulative effect. Pregnant women had normal percentages of potentially cytotoxic target binding cells, however, the relative number of lymphocytes that could kill bound targets (i.e. active NK cells) was significantly depressed in pregnancy when compared with normal controls (p less than 0.05). This diminished number of active NK lymphocytes was, however, normal in all phases of the lytic procedure. Interferon (IFN) treatment of effector cells in pregnant women in vitro did not alter target cell binding, but did increase the percentage of active NK cells. The level of stimulation by IFN was the same in pregnancy and control patients. The kinetics of response were the same for both cell populations and different doses of interferon caused a similar level of augmentation. In conclusion we suggest that the here demonstrated deficiency of active NK lymphocytes in pregnancy may represent a function of pregnancy associated immunoregulatory molecules which prevent a population of pre-NK cells to express their cytotoxic potential.

Cytotoxicity, Immunologic↗

Lymphocyte subsets in endometriosis.

Recent investigations suggested a possible immunologic etiology for endometriosis. To determine whether cellular immunity may be affected in patients with endometriosis, peripheral lymphocyte populations were investigated in 31 confirmed endometriosis patients and 22 control patients. No statistical differences in OKT3, OKT4, OKT8, OKM1, and OKTa1 cells could be observed. Total lymphocyte numbers were within normal ranges for both groups. Helper/suppressor ratios were not statistically different and were in a normal range for both groups. It is concluded that numeric differences in lymphocyte subpopulations represent only a very unlikely contributing factor in a potential immunologic etiology of endometriosis.

Antibodies, Monoclonal↗

Studies of natural killer cells in pregnancy. II. The immunoregulatory effect of pregnancy substances.

This study was performed utilizing a standard 51Cr-release cytotoxicity and a single cell assay against K-562 NK-sensitive target cells. Pregnancy sera and amniotic fluids, were found to decrease human natural killer (NK) activity. Pregnancy sera were able to inhibit overall NK activity of partly purified peripheral blood lymphocytes in a dose dependent fashion. However, the exposure of effector cells to concentrations higher than 20% did not further increase the serum's suppressive activity. Sera taken from preeclamptic pregnancies had a similar inhibitory effect as those from normal pregnancies. Amniotic fluid was found to be even more suppressive than pregnancy serum. Using a single cell cytotoxicity assay we determined that neither serum nor amniotic fluid affected potentially cytotoxic target binding cells ("pre"-NK). The relative number of conjugates with dead target was, however, significantly depressed under the influence of pregnancy serum and to an even greater extent by amniotic fluid. Both pregnancy substances were also able to decrease the number of conjugates with dead target in an interferon-augmented population of lymphocytes. Our investigation indicates that the suppressive effect of amniotic fluid and pregnancy serum on NK activity is based on a blocking effect exerted at the killing capability of the active NK cells.

Amniotic Fluid↗

Activity of natural killer cells in normal pregnancy and edema-proteinuria-hypertension gestosis.

Natural killer cytotoxicity of peripheral blood lymphocytes in normal pregnancy and edema-proteinuria-hypertension (EPH) gestosis was investigated and compared to natural killer cytotoxicity in lymphocytes of normal nonpregnant control donors. These lymphocytes were also compared for their ability to respond to interferon treatment in vitro. Natural killer activity was found to be only slightly decreased in normal pregnant women but was found to be increased in patients with EPH gestosis. Interferon treatment of peripheral lymphocytes caused strong enhancement of natural killer activity in lymphocytes of normal pregnant women but resulted in only weak activities in lymphocytes from patients with EPH gestosis. We consequently concluded that pre-natural killer lymphocyte subpopulations from patients with EPH gestosis have already been activated by a presently still unknown stimulator.

Adult↗

Concanavalin A agglutinability and immunoadherent properties of rat blastocyst.

Preimplantation rat blastocysts were examined in vitro for concanavalin A agglutinability and antigenic properties on the 5th day of development after flushing and after 24 h in culture, following regional differentiation. Differences were found between the two trophoblastic cell populations with regard to cell membrane receptors to concanavalin A. Immunoadherence hemagglutination tests show that the early trophoblast possesses antigenic properties, which are similarly present in the mural and polar cells of the early preimplantation blastocyst. With later differentiation in vitro, differences can be found between the two trophoblastic cell populations with regard to detectable surface antigens.

Agglutination Tests↗

Immunoregulatory mechanisms in pregnancy. II. Further characterization of suppressor lymphocytes induced by alpha-fetoprotein in lymphoid cell cultures.

Nonspecific suppressor cell (SPC) activity has been induced in vitro by preculturing splenocytes from normal mice in the presence of mouse amniotic fluid (MAF) and alpha-fetoprotein for 5 days or more. In adoptive transfer experiments in vivo, these AFP-precultured SPC were shown to reduce the humoral response of mice to sheep red blood cells and the cell-mediated cytotoxic response to allogeneic tumor cells. In mixing experiments in vitro, using freshly explanted splenocytes, the AFP-precultured splenocytes abrogated the generation of specific cytotoxic T-lymphocytes in primary mixed lymphocyte-tumor cell cultures. Supernatants of such precultured cells had at best only a marginal effect. These suppressor cells were found to be nylon-wool nonadherent and their effect could be almost completely abolished by treatment with anti-Thy-1, 2 serum plus complement. SPC precursors were found to be sensitive to cyclophosphamide (in vivo) and to hydrocortisone (in vivo and in vitro). At the same time, they are resistant to different doses of radiation.

Animals↗

Immunoregulatory mechanisms in pregnancy. 1. Evidence for the alpha-fetoprotein-induced generation of suppressor cells in vitro.

The generation of active suppressor cells has been induced in vitro by preculturing of splenocytes from normal mice in the presence of mouse amniotic fluid (MAF) and alpha-fetoprotein (AFP). By using freshly explanted splenocytes, addition of such precultured lymphocytes abrogated the generation of specific cytotoxic lymphocytes (CTL) in primary mixed lymphocyte cultures. Effective suppression can be induced only when the precultured cells are added within the first 48 hr of culture. These suppressor cells are nylon-wool nonadherent and their effect could be almost abolished by treatment with anti-Thy-1,2 serum plus complement. The precursors of the suppressor cells are sensitive to hydrocortisone and resistant to low doses of radiation. The induction of suppressor cells by AFP may be one of the mechanisms resulting in deviant immune response during pregnancy and in the newborn.

Animals↗

Observations on some immune properties of preimplantation rat blastocysts.

Rat blastocysts after 3, 24 or 72 hours in culture, were exposed to antiserum against rat embryo and mouse placenta in the presence of complement. The concomitant exposure damaged the trophoblastic cells and the inner cell mass. Differences were not observed in the nature and strength of the damage between blastocysts with or without zona pellucida. When the cultured blastocysts were exposed first to antisera and only later to complement, the damage seemed to be selective. In the 3 and 24 hour cultured blastocysts, only the trophoblastic cells were destroyed but not the inner cell mass. In the 72 hour cultures, the damage was inflicted to all cells including the inner cell mass, exposed after spreading of trophoblastic cells. The anti-rat embryo serum and the anti-mouse placenta serum had similar effects in low dilutions. In high dilution, the anti-rat embryo serum was more potent. Isolated inner cell masses were cultured up to 72 hours but did not attach to the dish nor spread. Nevertheless, the cells survived, proliferated and differentiated into an outer layer of seemingly endodermal cells.

Animals↗

Renal damage following transplantations of heterologous placental tissue.

Immunological interrelations between placenta and kidney have become a matter of interest with regard to the pathogenesis of preeclampsia. Kidney morphology of Lewis rats was studied following repeated transplantations of heterologous or syngeneic placental tissue. In most of the heterologous placenta-recipient animals, diffuse severe glomerular lesions were found, similar to those seen in women with preeclampsia. In the strongly responding recipients, endothelial cell swelling, narrowing of capillary lumina and proliferation of mesangial matrix were observed. Patchy areas of fluorescence associated with dense IgG deposition, as well as fibrin deposits demonstrated in the affected glomeruli, were correlated with histologic changes. The use of syngeneic placenta as a transplant did not cause histological or immunohistological changes. These findings support the view that differences in histocompatibility antigens between mother and fetus may be involved in the pathogenesis of the nephropathy in preeclampsia.

Animals↗

Cellular hyperreactivity to placenta in toxemia of pregnancy.

It is generally assumed that maternal immune response may be involved in some pathological conditions of pregnancy, such as toxemia. The activity of cell-mediated immunity to placenta was studied in women with gestosis. The leucocyte inhibition technique was employed to test reactivity of peripheral blood leucocytes from postpartum women. The results indicated that leucocyte migration was significantly inhibited in the presence of placental microsomal fraction when blood from toxemic women was used. Thus, about 87% out of 30 studied cases of toxemia showed positive results. At the same time, in only 22% of women with uncomplicated pregnancy was such a positive leucocyte migration inhibition test found. There was no correlation between the severity of the toxemic symptoms and the extent of inhibition. In further experiments the leucocyte migration inhibition test with the microsomal fraction antigens from cadaver kidneys was performed; only 1 out of 6 patients showed positive leucocyte migration inhibition. These findings may suggest that the normal status of the mother is altered towards cellular hyperreactivity to placental antigens in toxemic pregnancy.

Female↗

In vitro anti-kidney effect of lymphocytes in experimental immunization to placental antigens.

The lymph node and spleen lymphocytes of placenta-sensitized guinea pigs were tested for their ability to destroy kidney monolayer. It was shown by microcytotoxicity assay that these sensitized lymphoid cells killed target monolayer at different effector/target cell ratios. About 35% of kidney cells were destroyed when sensitized lymph node cells were added at a ratio of 500: 1, and 50% at a ratio of 1000:1. Immunized spleen cells produced approximately the same results. No significant cytotoxicity was measured when placenta-sensitized lymphocytes were added to nonrelated mouse skin fibroblasts. In order to exclude the possibility of participation of species-specific antigens in this experimental model, placenta-sensitized lymphocytes were added to L-cell monolayer in the presence of kidney antigens or mouse normal serum (a carrier of species-specific determinants). An extensive cytotoxic effect was observed in the presence of kidney antigens, while addition of mouse normal serum did not induce significant target cell lysis. The cross-reactivity of the cytotoxic ability of placenta-sensitized lymphocytes may indicate that cell-mediated immunity can be involved in the pathogenesis of nephropathy in toxaemic pregnancies, accompanying sensitization by placental antigens.

Animals↗

Studies on sperm antigenicity. IV. Lymphocyte cytotoxicity in cell-mediated response to homologous spermatozoa.

In the presence of specific antigen, lymph node cells from Rockefeller strain guinea pigs with delayed hypersensitivity to homologous spermatozoal antigen produced progressive destruction of L929 cell monolayers. This effect was measured by counting surviving target cells removed from Leighton tubes by trypsin treatment as well as by standard cell counts in microplates. The cytotoxic effect was immunologically specific since neither sperm-sensitized lymphocytes in presence of unspecific antigen nor normal lymph node cells with guinea pig sperm, induced target cell destruction. The effect required an antigen concentration equal to, or greater than, 70 micrograms protein/ml. A ratio of 100:1 of sensitized lymphoid cells to target cell was found to be optimal. L-cell lysis could be demonstrated at day 14 and reached its peak on day 21 after immunization. A high level of correlation between lymphocyte cytotoxicity and macrophage migration inhibition was found. The role of lymphocyte cytotoxicity in cell-mediated immunity to spermatozoa is discussed as one of the possible mechanisms leading to destructive changes in the testes.

Animals↗

The effect of alpha-fetoprotein on the growth of placental cells in vitro.

Cell cultures of early mouse placentae were studied in the presence of mouse amniotic fluid or isolated alpha-fetoprotein (AFP). Four cell types were observed: polygonal cells, giant cells, small round cells and fibroblasts. The number of polygonal cells increased in placental cultures in the presence of amniotic fluid or AFP, suggesting de novo formation and proliferation in vitro. These preparations were found to stimulate the DNA synthesis in polygonal cells, as demonstrated by 3H-thymidine labelling experiments. Polygonal cells also show a significant increase in 3H-leucine incorporation, indicating more active protein synthesis under the effect of amniotic fluid or AFP. These data suggest that AFP may be one of the fetal factors promoting trophoblastic differentiation.

Amniotic Fluid↗