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E Sabbadini

Publications and source records attributed to E Sabbadini.

At least 19 recordsLinked to original sources
PubMed1992

Endocrine control of the immunosuppressive activity of the submandibular gland.

Extracts of the submandibular gland (SMG) of rats contain fractions that stimulate the in vitro proliferation of Con A-treated lymphocytes. One of the stimulatory fractions was also shown to induce in vivo immunosuppression in rats and mice in several experimental models. Since many other biologically active factors of the SMG had been found to be hormone dependent, we investigated the effects on the immunosuppressive factor of hypophysectomy (Hx) and of hormonal reconstitution in male Fischer rats. Hx induced a marked atrophy of the SMG together with an almost complete disappearance of both the in vitro lymphocyte-stimulating activity and the in vivo immunosuppressive activity, the latter assayed with the contact sensitivity reaction in mice. The treatment of the Hx rats with pituitary hormones demonstrated that prolactin (PRL), thyroid stimulating hormone (TSH), and luteinizing hormone (LH) induced a significant reconstitution of these biological activities, growth hormone led to the recovery of the lymphocyte-stimulating activity but not of the immunosuppressive activity, while follicle-stimulating hormone, and adrenocorticotropic hormone did not induce any recovery of these biological activities. In view of the positive results obtained with TSH and LH further experiments were done to compare the effects of thyroid and sex hormones with those of PRL. The results demonstrated that testosterone and thyroid hormones induced significant recovery of the lymphocyte-stimulating and the immunosuppressive activity. The combination of these two hormones with PRL produced the most effective results. On the other hand, estrogens and progesterone had no significant effects. These results confirm the effectiveness of androgens and thyroid hormones in stimulating the production of biologically active factors by the SMG. Moreover, they demonstrate that PRL, a hormone not previously considered to increase the activity of the SMG, stimulates the production of immunoregulatory factors in Hx animals.

Adrenocorticotropic Hormone↗
PubMed1992

Identification of immunosuppressive fractions from the rat submandibular salivary gland.

It had previously been suggested that the submandibular gland (SMG) of mice and rats may contain in vivo immunosuppressive factor(s). To identify such factor(s), we used a multi-step purification procedure of rat SMG extracts. Gel filtration chromatography of the SMG crude extract resulted in two pools of fractions with significant effects on lymphocyte reactivity in the in vitro concanavalin A (Con A) bioassay. Of these two pools, only the one with lower molecular weight resulted in the prolongation of murine skin allograft survival, the suppression of the delayed-type hypersensitivity (DTH) response to picryl chloride and the decrease in number of direct (IgM) plaque-forming cells against sheep red blood cells. Fractionation of this low molecular weight (LMW) pool through hydrophobic interaction chromatography resulted in three protein fractions designated A, B and C. Of these fractions only fraction A produced significant suppression of the DTH response. Further purification of fraction A with anion exchange chromatography produced two fractions with immunosuppressive activity in the DTH response. One fraction demonstrated on SDS-PAGE a single component of 40,000 MW, while the other had two components of 30,000 and 40,000 MW respectively.

Animals↗
PubMed1989

Purified human early pregnancy factor from preimplantation embryo possesses immunosuppresive properties.

This study was undertaken to determine whether early pregnancy factor secreted by preimplantation embryos has immunosuppressive properties. Human early pregnancy factor was purified from embryo growth media of in vitro fertilized ova with ion-exchange and gel filtration chromatography. During each step of purification the fractions were tested for (1) early pregnancy factor activity with the rosette inhibition assay, (2) immunosuppressive properties with a concanavalin A-stimulated lymphocyte proliferation assay, and (3) purity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Results indicate that (1) human early pregnancy factor has a basic molecular weight of 14 kd, (2) early pregnancy factor has immunosuppressive activity, (3) polymers of early pregnancy factor also appear to be present in the embryo growth media, and (4) immunosuppressive factors other than early pregnancy factor are also secreted by preimplantation human embryos. Early pregnancy factor and other factor(s) produced by the preimplantation embryo may play a role in suppressing maternal cellular immune responses, thereby preventing maternal rejection of the embryo.

Blastocyst↗
PubMed1986

Inhibition of interleukin 1 activity by a factor in submandibular glands of rats.

With the sequential use of ammonium sulfate precipitation, gel filtration and chromatofocusing, we have partially purified from extracts of the submandibular glands of rats a factor (referred to as submandibular gland's immunosuppressive factor or SMG-ISF) capable of inhibiting the in vitro proliferation of mitogen- and antigen-stimulated murine lymphocytes. The semi-purified suppressor fractions had an isoelectric point of 4.4 to 4.5 and consisted of at least three molecular species. These active fractions suppressed the mitogenic effects of Concanavalin A phytohemagglutinin, and lipopolysaccharide. In vitro immune reactions such as the mixed lymphocyte culture MLC reaction and the production of cytotoxic T lymphocytes (CTL) across major histocompatibility barriers in mice were also suppressed. These in vitro immunosuppressive effects required the addition of the suppressor fractions early after the initiation of the cultures and were reversed if the factor was removed from the cultures at least 48 to 72 hr before the completion of the assays. The active fractions did not affect the proliferation of CTLL 2 cells induced by interleukin 2 (IL 2), but inhibited the mitogenic and co-stimulatory effects of IL 1 on mouse thymocytes, and in this effect showed a dose-response relation suggestive of a competitive mechanism. These characteristics of SMG-ISF indicate a specific inhibition of the activity of IL 1.

Animals↗
PubMed1985

Effect of Bacillus Calmette-Guérin on the in vitro generation of cytotoxic T lymphocytes. II. Role of interleukin-1-like factors and of soluble suppressor factors.

The injection of BCG vaccine in C57BL/6J mice results in the suppression of the generation of cytotoxic T lymphocytes (CTL) in mixed lymphocyte cultures (MLC) and of mitogenic reactions to concanavalin A (Con A). Suppression is mediated by macrophage-like suppressor cells. Since previous work had indicated that suppression involved the inhibition of the production of interleukin-2 (IL-2), the effects of BCG on interleukin-1 (IL-1), a monokine required for IL-2 production, were investigated. It was found that the release of IL-1-like activity in spleen cell cultures stimulated with LPS or Con A was increased by previous BCG treatment of the cell donors. In MLC, the release of IL-1-like activity was also increased by BCG. However, the detection of IL-1-like activity in MLC supernatants was prevented by the presence of a suppressor factor. In this case, the IL-1-like activity could be separated with gel filtration from the suppressor factor which had higher molecular weight. The production of IL-1-like activity by CBA/J spleen cells, which are not suppressed by BCG, was not significantly different from that of C57BL/6J cells, which are markedly suppressed. Moreover, the addition of IL-1 to the BCG-suppressed cultures not only did not restore normal reactivity, but actually further suppressed CTL formation. It was concluded that BCG-induced suppression cannot be attributed to decreased IL-1 activity. The suppressor factor discovered during these investigations may have a role in this type of suppression.

Animals↗
PubMed1985

Suppression and enhancement of in vitro lymphocyte reactivity by factors in rat submandibular gland extracts.

The addition of crude extracts from rat submandibular (SM) glands to murine spleen and lymph node cell cultures stimulated with concanavalin A (Con A) induced either suppression (at high concentrations) or further stimulation (at lower concentrations) or further stimulation (at lower concentrations) of proliferative activity. Gel filtration of the extracts revealed that suppressive activity was due to factors of molecular weight in the 50,000-96,000 range, while stimulation was due to factors in the 13,000-35,000 molecular weight range. The suppressor activity of the higher molecular weight fractions was not due to a reduction of cell viability or of the uptake of tritiated thymidine. This was demonstrated by the fact that the addition of IL-2 to the cultures completely reversed the suppressive effect. Further fractionation of the suppressive and of the stimulatory gel filtration fractions with the chromatofocusing technique led to the identification of a single fraction with suppressor activity and of multiple discrete fractions with stimulatory activity.

Animals↗
PubMed1982

Mechanisms of BCG action. I. The induction of nonspecific helper cells during the potentiation of alloimmune cell-mediated cytotoxic responses.

Donor mice were treated IV with BCG and after various time intervals the spleens from these animals were injected into syngeneic recipients which were simultaneously challenged with an allogeneic tumour. The spleen cells from the BCG-treated donors, but not untreated donors, conferred on the recipients an ability to induce a potentiated CMC reaction against the tumour. The transference of BCG-induced potentiating activity could not be explained by the transference of viable BCG organisms, but was mediated by a cell that was anti-Thy.1-sensitive, silica-resistant, plastic-nonadherent, and nylon wool-adherent, and was sensitive in vivo to anti-thymocyte serum but resistant to hydrocortisone. By the use of congenic strains of mice that differed at the Thy.1 allele, it was shown that the cells responsible were not precursors of the cytotoxic lymphocytes but were cells that produced an amplification of the response of the recipient host's precursor cytotoxic T cells.

Animals↗
PubMed1981

Variations in the intensity of BCG-potentiated alloimmune anti-tumor responses: the differential stimulation of T-cell subpopulations.

The interexperimental variation often observed following the repeated monitoring of immune phenomenon was analysed using the alloimmune cellular response that developed in the spleens of B6AF mice following a challenge with Mastocytoma P815-X2 and intervention with BCG. The response, mediated solely by T cells, could be defined in terms of the involvement of nylon-wool adherent and nonadherent T cells. The relative contribution of each cell type to the response was found to vary considerably and could be use to define the interexperimental variation. Hence when a given treatment resulted in a poor response, the major contributors were nonadherent to nylon-wool, while when the same treatment yielded a good response, adherent cells became the predominant contributors. It was concluded that the inter-experiment variations observed here were a biological event, rather than an experimental artefact, being a function of the relative contribution of different T-cell subpopulations.

Adjuvants, Immunologic↗
PubMed1979

Dose-dependent adjuvant effects of Bacillus Calmette-Guérin on tumor immunity in Lewis rats.

The study was undertaken of the ability of Bacillus Calmette-Guérin (BCG), used in combination with a live tumor cell vaccine, to potentiate systemic antitumor immunity in rats. BCG was administered in two injections, with the first one given i.v. and the second one given intradermally mixed with the tumor cell vaccine 12 days later at the time of implant of an s.c. tumor, which served to monitor antitumor immunity. Both these BCG injections were necessary to obtain maximal protection measured in terms of increased survival rates of the rats and of decreased tumor growth rates. The dose of BCG in both the first and second injections was critical for optimal protection, since low doses (125 to 250 micrograms) afforded protection, while higher doses (over 1500 micrograms) decreased or abolished the protective effect. These results strongly suggest that BCG, only if administered under the appropriate conditions, is able to potentiate systemic tumor immunity and to provide a significant level of protection for a tumor-bearing animal.

Animals↗
PubMed1978

Effect of BCG on alloimmune cell-mediated cytotoxicity in (C57BL/6Jfemale x A/Jmale)F1 mice. I. Effect of different BCG treatments on cytotoxicity mediated by T-cells and macrophages.

The effect of BCG on the development of cell-mediated cytotoxicity (CMC) in the spleens of allogeneic tumor-bearing female (C57BL/6Jfemale x A/Jmale)F1 mice was studied. BCG-treated tumor-bearing animals elicited a stronger CMC response than did the untreated tumor-bearing animals. Furthermore, the degree of activation was dependent on the time, route of injection, and dose of BCG. Therefore, if the BCG was administered at suboptimal conditions, a less marked stimulation of the CMC resulted. A combination of a high BCG dose given iv 12 days before implant of P815 tumor cells and a low, second dose given at the time of implant produced the most marked activation of the CMC response. By the use of in vitro technique, the specific CMC was mediated mostly by T-cells, with macrophages making a less significant contribution.

Animals↗
PubMed1978

Effect of BCG on alloimmune cell-mediated cytotoxicity in (C57BL/6Jfemale x A/Jmale)F1 mice. II. Correlation with BCG activity in syngeneic tumor systems.

The effectiveness of selected BCG regimens to produce an activation of cell-mediated cytotoxicity (CMC) in an allogeneic tumor system was compared with its ability to cause tumor regression in syngeneic tumor systems. In the tumor system selected in both inbred LEW rats and inbred C57BL/6J and (C57BL/6Jfemale x A/Jmale)F1 mice, a correlation was observed in that BCG treatments that caused marked CMC activation in the allogeneic tumor systems also effectively caused tumor regression and increased animal survival in syngeneic systems. It was concluded that the allogeneic CMC reaction can be used to predict the capacity of BCG to cause tumor rejection.

Animals↗
PubMed1977

Effect of different doses of BCG on an allogeneic cell-mediated antitumor response in mice.

The effect of BCG on the development of cell-mediated cytotoxicity (CMC) in the spleens of allogeneic tumor-bearing (C57BL/6 X A)F1 mice was studied. BCG-treated tumor-bearing animals elicited a stronger CMC response than did the untreated tumor-bearing animals. Furthermore, the degree of activation was dependent on different doses of BCG, so that if the BCG was administered at doses above or below the optimum dose, a less marked stimulation of the CMC resulted. The combination of BCG given before the tumor implant plus an intratumor inoculation resulted in a significantly higher CMC than did either treatment alone.

Animals↗
PubMed1977

Regulation of cell-mediated cytotoxicity. III. Synergism of cortico-resistant with anti-thymocyte serum-resistant splenic T cells in the generation of cytotoxic lymphocytes in graft-vs-host reactions.

Lethally irradiated F1 hybrid mice were given an i.v. injection of parental strain spleen cells. Six days later, their spleen cells were used as the effector cells to measure the in vitro cell-mediated cytotoxicity (CMC) of the parental cells. The treatment of the donors with hydrocortisone resulted in a marked decrease of the capacity of their spleen cells to produce a CMC reaction, whereas the treatment with antithymocyte serum (ATS) resulted in an almost complete loss of such activity. The mixing of spleen cells from hydrocortisone-treated parental donors with the spleen cells from ATS-treated parental donors before injection resulted in a synergistic amplification of the cytotoxic response. The anti-Thy-1 serum treatment of either spleen cell population abolished the synergism completely. These results indicate that cortico-resistant T cells act as precursors of cytotoxic lymphocytes and that ATS-resistant T cells produce an amplification of their reaction.

Animals↗
PubMed1976

Cytotoxicity in graft-versus-host reaction. II. Lysis of target cells of parental genotyppe by F1 hybrid macrophages.

Graft-versus-host (GVH) reactions were induced in adult F1 hybrid mice with the i.p. injection of parental strain spleen cells. Peritoneal exudate and spleen cells of the F1 hybrids taken 8 days after the induction of GVH reaction had a nonspecific in vitro cytotoxic effect which was measured by using 51Cr-labeled target cells of parental genotype. The cytotoxic cells in the peritoneal exudates were shown to be macrophages which adhered to plastic surfaces and were sensitive to the toxic action of crystalline silica particles. Moreover, the injection of partially purified syngeneic macrophages into the F1 hybrids undergoing GVH reactions increased the cytotoxic activity of the peritoneal exudate cells obtained from these animals. These results suggest that during GVH reaction host macrophages are activated into a state of nonspecific cytotoxicity.

Animals↗
PubMed1974

Regulation of cell-mediated cytotoxicity. I. Augmentation of cell-mediated cytotoxicity induced by radiation.

Mice were treated with sublethal and midlethal doses of irradiation (500-700 rads) and injected intravenously with allogeneic or semiallogeneic F(1) hybrid spleen cells. The cytotoxicity developed by their spleen cells was measured with the lysis of (51)Cr-labeled target cells and was found to be stronger (although delayed in time) than the cytotoxic activity of spleen cells from nonirradiated mice. The injection of syngeneic thymus or spleen cells in the irradiated mice after their treatment with allogeneic spleen cells exerted a suppressor activity, i.e., reduced the level of cell-mediated cytotoxicity (CMC). The majority of effector cells involved in the modified CMC response of irradiated mice was shown to be of host origin and lysed specifically target cells of the same genotype as the donor. A small percentage of the cells obtained from the spleens of irradiated recipients of allogeneic spleen cells was composed of donor cells which lysed specifically target cells of the same genotype as the host. These results demonstrate that the precursors of the cytotoxic cells responsible for target cell lysis are relatively radioresistant and suggest that their response is regulated by radiosensitive thymus-dependent cells.

Animals↗