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Biomedical subjects

R Kinsky

Publications and source records attributed to R Kinsky.

At least 19 recordsLinked to original sources
PubMed1995

Alloimmunization against well defined polymorphic major histocompatibility or class I MHC transfected L cells antigens can prevent poly IC induced fetal death in mice.

METHOD: It is possible to induce increased fetal resorption in a number of inbred murine matings by injecting Poly (I) Poly (C12U) 3.5 days postconception, a maneuver associated with natural killer-mediated damage to the feto placental unit such as occurs in spontaneous fetal resorptions. RESULTS: We show here that alloimmunization can block this effect. In addition, maternal immune responses induced by alloimmunization against isolated mutant class I or class II, as well as by immunization with class I MHC alloantigens (Kd) transfected L cells are sufficient to restore normal fetal viability. It is not necessary that the maternal immune response be specifically directed against paternal alloantigens fr the fetal protection to ensue, since the effect occurs in inbred matings when the mother is immunized against unrelated class I or class II alloantigens. As in previous studies conducted in the murine species, not all MHC alloimmunizations are protective. In addition, as control, immunization with a monomorphic class I MHC molecular (37), transfected L cells, sheep red blood cells or hen egg lysozyme is without effect. CONCLUSION: These results indicate that defined MHC antigens can mediate fetal protection from induced fetal resorption, and suggest that one driving force in promoting MHC antigen polymorphism in mammals is their capacity to confer protection from NK mediated fetal demise.

Animals↗
PubMed1995

In vivo immunosuppressive effects of recombinant ovine interferon-tau (trophoblastin): r.oTP (r.oIFN-tau) inhibits local GVH reaction in mice (PLN assay), prevents fetal resorptions, and favors embryo survival and implantation in the CBA/J x DBA/2 mice combination.

PROBLEM: Ovine trophoblastin protein, be it natural or recombinant (oTP,r.oTP), a member of the tau interferon family (r.oIFN-tau), has been shown to possess immunosuppressive properties in vitro. It acts as a cytostatic agent across species. Indeed, it was immunosuppressive when tested on human and murine lymphocytes in a variety of in vitro immune assays, as it is also on syngenic (ovine) lymphocytes. METHODS: In the present paper, we first verified that this property to act across species also occurred in vivo assays; r.oTP was able to down regulate a local GVH reaction assay (PLN assay) in mice. We then took advantage of these properties of r.oTP to investigate its in vivo effects during murine pregnancy as there is no ovine equivalent of the murine CBA/J x DBA/2 resorption prone mating combination. RESULTS: When given in the postimplantation period, r.oTP drastically boosted resorptions in the CBA/J x DBA/2 matings, as did murine recombinant gamma interferon. However, the same r.oTP treatment in the peri-implantation period resulted in a reduction in resorptions in this spontaneous abortion system. CONCLUSION: The data suggested that r.oTP might have acted more by favouring implantation and embryo survival than by preventing the resorption process itself. The mechanisms possibly underlying these effects, as well as the putative uses of r.oTP evolving from these data, are discussed.

Age Factors↗
PubMed1993

Suppression of local and systemic GVHR by supernatants from human choriocarcinoma cell lines.

Graft versus host reaction (GVHR) and host versus graft reactivity during pregnancy share at least some cellular pathways. Immunosuppression mediated by placental suppressor factors may actively contribute to the survival of the conceptus in the immunocompetent mother. We have previously reported that supernatants from human choriocarcinoma cell lines inhibit mitogen-activated and antigen-activated proliferation of lymphoid cells. From this perspective, we investigated the capacity of supernatants from human choriocarcinoma cell lines (HCS) to suppress in vivo graft versus host reactions in mice. HCS was tested for its ability to block both local as well as systemic GVHR induced by the injection of parental cells into F1 mice. HCS mediates profound suppression of acute and chronic GVHR. These results confirm that human choriocarcinoma cell lines secrete a potent immunosuppressive factor(s) which can efficiently modulate immune responses in vivo.

Animals↗
PubMed1992

The proportion of symmetric and asymmetric IgG antibody molecules synthesized by a cellular clone (hybridoma) can be regulated by placental culture supernatants.

The purpose of the present work was to establish whether the placenta is producing factors favoring an increased synthesis of asymmetric IgG antibodies which are known to assume a protective effect upon paternal antigens to which they largely are specific. In this way they can contribute to fetal survival in the maternal uterine environment. The hybridoma cell lines OKT8 (anti-CD8) and 112B4 (anti-DNP) were used in this respect since they synthesized both symmetric and asymmetric molecules of the IgG2a and IgG1 subclasses, respectively, murine isotypes in which anti-paternal antibodies have been detected. The cells were cultured in RPMI 1640 medium supplemented with 10% BCS and different amounts (5, 10, and 20%) of human placental supernatant. After incubation for 3 days at 37 degrees C in a humid chamber containing 5% CO2 the cells were centrifuged and the antibodies were obtained from the culture medium by a purification procedure involving precipitation at 50% ammonium sulfate saturation followed by DEAE-cellulose chromatography. Symmetric and asymmetric antibodies were separated by Con A-Sepharose affinity chromatography, the latter lectin retaining selectively only asymmetric IgG molecules. Both OKT8 and 112B4 hybridomas presenting a stable background synthesis of 15-17% of asymmetric antibodies have shown an increased level reaching 27-28% of these molecules in the presence of 5-10% placental supernatant added to the RPMI 1640 culture medium. These results clearly show that placental factors can up-regulate efficiently the synthesis of asymmetric IgG molecules of different isotypes secreted by plasma cells.

Animals↗
PubMed1991

Immunoactive products of human placenta. IV. Immunoregulatory factors obtained from cultures of human placenta inhibit in vivo local and systemic allogeneic and graft versus-host reactions in mice.

We have shown in previous reports that human placental supernatants (HPS) display a variety of immunoregulatory properties in vitro. Here we report that these supernatants are able to suppress the ability of murine splenocytes to evoke an allogeneic reaction in the popliteal lymph node (PLN) assay, as well as their capacity to induce both local (popliteal lymph node swelling) as well as systemic chronic or lethal graft-versus-host reactions. Those results are discussed in the light of the potential use of HPS in the control of transplantation immune reactions as well as in the regulation of xenogeneic pregnancies, as the murine system that was used proved that the material exerted an effect across a species barrier.

Animals↗
PubMed1991

Complete Freund adjuvant treatment of pregnant females influences resorption rates in CBA/J x DBA/2 matings via progesterone-mediated immunomodulation.

Treatment of pregnant CBA/J females with CFA at day 0.5 and 7.5 of pregnancy significantly reduced the fetal resorption rates from 45% to 29% (P less than 0.05). Supernatants of progesterone-treated spleen cells from CFA treated CBA/J females pregnant of DBA/2 males significantly reduced natural cytotoxicity, while those of untreated identically pregnant mice had no effect. Supernatants of CFA-treated virgin mice blocked natural cytotoxicity to the same extent as those of CFA-treated pregnant mice. These data suggest that nonspecific immunostimulation induces progesterone receptors in spleen cells of CBA mice and that these receptors allow a progesterone dependent suppressive pathway to exert an antiresorptive effect.

Animals↗
PubMed1990

A progesterone-induced blocking factor corrects high resorption rates in mice treated with antiprogesterone.

Earlier we showed that because of the presence of functional progesterone receptors, lymphocytes of healthy pregnant women produced an immunomodulatory protein in the presence of progesterone, whereas those of nonpregnant persons did not. Progesterone-treated murine pregnancy lymphocytes release a similar factor. The present study reveals the biologic significance of this finding. Treatment of BALB/c mice that were 8 days pregnant with a progesterone receptor blocker (RU 486) resulted in 100% resorption of the fetuses. Simultaneous administration of the supernatant from progesterone-treated murine pregnancy spleen cells restored the resorption rate to the original 6% observed in untreated control animals. These data suggest that functional lymphocytic progesterone binding sites are needed for the maintenance of normal pregnancy. Because of the blockage of progesterone receptors and the consequent inability of the lymphocytes to produce the progesterone-induced blocking factor, abortion is initiated by immune factors. The fact that administration of the preformed blocking factor counteracted the effect of antiprogesterone treatment suggests that progesterone-mediated immunosuppression is needed for the maintenance of normal gestation.

Abortion, Induced↗
PubMed1990

A murine model of NK cell mediated resorption.

There is increasing evidence that some models of immunologically mediated murine embryo demise involve nonspecific lytic effector cells. In this paper, we use two double stranded synthetic RNAs, known as potent interferon inducers and NK cell activators, the Poly (I). Poly (C) and the less toxic Poly (I). Poly (C12U). These polynucleotides enhance fetal resorption rates in both resorption prone and none-resorption prone strains of mice. We have studied the kinetics of the phenomenon, and observed an anti-implantation-like effect of early injection during early pregnancy. The abortifacient effects can be adoptively transferred to naive recipients by spleen cells from Ds RNA injected donors. Such effects are abrogated if the cells are pretreated with anti-NK cell antiserum. The relevance of these findings to the survival of the conceptus is suggested.

Animals↗
PubMed1990

The effect of a progesterone-induced immunologic blocking factor on NK-mediated resorption.

Transfer of spleen cells from poly (I)-poly(C12U)-treated Balb/c mice to 6.5-days-pregnant Balb/c mice significantly increased the resorption rate (P less than 0.01) from 11% to 48%. The supernatant of progesterone-treated spleen cells from pregnant C3H mice abrogated the effect of spleen cell transfer. We conclude that by blocking NK activity in vivo, the progesterone-induced blocking factor favors the maintenance of pregnancy.

Animals↗
PubMed1988

Antigen-specific modulation of graft-versus-host reactions by two distinct placental factors.

We have previously shown that two distinct mouse placental fractions (PF) are potent immunomodulators in vivo. A 40 kDa PF induces a marked decrease of plaque forming cell (PFC) responses, while a 60 kDa PF increases them. Both effects are specific for the priming antigen. In the present study, these two PF are assayed on a cell-mediated response to allogeneic cells, i.e. in a local graft-versus-host reaction (LGVHR). Mice were primed with allogeneic cells in the presence of various amounts of the 40 kDa or 60 kDa PF, or liver extract (LE) as control. Six days later, their spleen cells were injected into the footpads of F1 recipients. Precise dose-response curves were established and the kinetics of the GVH response were carefully followed. Parallel with the modulation of PFC responses, the 40 kDa PF caused a potent inhibition of the LGVHR, while the 60 kDa PF greatly enhanced it. Both effects were specific for the alloantigens injected with the PF. Furthermore, we showed that these modulations were observed whatever the intensity of the GVH reaction, which varied according to the number of primed spleen cells transferred. This report also demonstrates that these PF can be greatly enriched by passage over affinity columns made of insolubilized lectins. The 40 kDa PF is retained on and can be eluted from columns of insolubilized concanavalin A (Con A) or wheat germ agglutinin (WGA), which indicates that it is a glycoprotein. Conversely, the 60 kDa PF does not bind to any of the above lectins and is probably not a glycoprotein. This biochemical purification step is also a good procedure for obtaining an even cleaner separation of the two fractions from each other. Thus, this paper demonstrates that both PF have important regulatory properties on specific cellular immune responses.

Adjuvants, Immunologic↗
PubMed1988

Effects of silica pretreatment on allogeneic tumour growth in mice treated with lentil lectin, spleen extract or alloantisera.

The effect of silica treatment (5 mg intravenously) on tumour growth was studied with regard to three types of immunosuppression induced by: lentil lectin (LCA), spleen cell extract (SE) (active enhancement), and alloantiserum (AAS) (passive enhancement). Two experimental tumours were used, which differ in their sensitivity to humoral antibodies. CBA mice were challenged with Sa 1 (A) tumours and BALB/c mice with EL-4 (C57BL/6) lymphomas. The results indicate that silica treatment caused a time-dependent promotion of tumour growth. In passive enhancement, tumour growth promotion by silica treatment was obtained in both tumour systems. When silica was given along with LCA or SE, the two combined treatments had no enhancing effect on Sa 1 targets and enhancing effects on EL-4. The different behaviour of the two graft-recipient combinations is discussed in the light of the inherent properties of both experimental tumours and of the donor-recipient relationships.

Animals↗
PubMed1988

Lack of differential sensitivity of normal hematopoietic stem cells and murine lymphoblastic leukemic cells to a lysosomotropic agent, N-dodecyl morpholine.

The effect of N-dodecyl morpholine (NDM), a lysosomotropic compound, on the clonogenic capacity of GK15, Sp2.0, Hb131, and L1210 lymphoblastic tumor cells and CFU-GM and CFU-S progenitor cells from DBA/2 mice was measured in order to evaluate the potential use of this compound for the purging of tumor-contaminated bone marrow (BM) in autologous BM transplantation. The growth of clonogenic tumor cells from all of the tested cell lines was inhibited with doses of NDM that also killed 100% CFU-GM and CFU-S, and no optimal dose could be found in this animal model to purge marrow while sparing sufficient stem cells to ensure engraftment in syngeneic BM transplantation.

Animals↗
PubMed1981

Separation of tumor-seeking small lymphocytes and tumor cells using Percoll velocity gradients.

Using the polyoma virus-induced ascitic SEYF-a tumor, we evaluated isopycnic and velocity sedimentation gradients of Percoll as methods for separating tumor-seeking lymphocytes and tumor cells. It was established that the velocity sedimentation method is suitable for separation of small lymphocytes lodging within the SEYF-a tumor. This was confirmed by a serological analysis of the separated SEYF-a cell population. The results of this study strongly support our previously reported data demonstrating the in vivo coating of the tumor cells proper with potentially cytotoxic antibodies.

Animals↗
PubMed1977

Immune status of mice tolerant of living cells. III. Presence and evolution of cells cytotoxic to the tolerated strain.

Spleen cells from CBA mice neonatally rendered highly tolerant to A/Jax (keeping a skin graft in perfect shape for more than 1 year and without detectable hemagglutinating or cytotoxic antibodies) contain cells cytotoxic for YAC 222 (A/Jax) in Cr release assay. The degree of the cytotoxicity depends on the age of the mouse, following a curve lower than, but parallel to, the one followed by the cytotoxicity of cells from CBA rendered immune by injecting them with A/Jax cells 1 week previously. The maximum of the cytotoxicity curve is reached during the 9th and 10th weeks. Normal CBA cells themselves are moderately cytotoxic to YAC 222. This "natural" cytotoxicity, significantly less intense and presumably directed against Moloney virus-related determinants, does not follow the same time pattern. The cytotoxic indices from both immune and tolerant cell populations are significantly reduced by CBA and anti-A/Jax immune serum. The tested sera of the tolerant mice did not contain hemagglutinating or in vitro-blocking antibodies in the Cr release assay (only the sera from unsuccessfully treated mice, having rejected their skin grafts, had some degree of blocking activity). However (and in agreement with previous experiments), these sera often contained synergistic hemagglutinins and in vivo enhancing properties of A/Jax tumors (Sal) grafted on CBA recipients.

Age Factors↗