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B Leshem

Publications and source records attributed to B Leshem.

28 records · Page 2Linked to original sources
PubMed1986

Bone marrow transplantation with T-cell-depleted grafts. I. Reconstitution of immunohemopoietic functions in lethally irradiated mice transplanted with unseparated or T-cell-depleted syngeneic bone marrow grafts.

The potential role of donor's mature T lymphocytes on the recovery of various immunological functions and hematopoiesis was investigated in lethally irradiated BALB/c mice by studying reconstitution with normal, as compared with T-cell-depleted, syngeneic marrow grafts. Recovery of total, as well as mononuclear, peripheral white blood cell counts, platelets, hemoglobin levels, proportion of Thy 1.2+ cells, responses to concanavalin A, phytohemagglutinin and lipopolysaccharide, mixed lymphocyte response, cell-mediated lympholysis response, anti-SRBC agglutinins and natural killer activity were basically similar in recipients of unmanipulated (as compared with T cell depleted) syngeneic marrow grafts. The data suggest that in a syngeneic murine bone marrow transplantation setting, mature donor T lymphocytes do not seem to play a major role in immunohemopoiesis. Normal T cell number and T-cell-dependent immune function can be readily regenerated out of the stem cell reservoir of adult donors following transplantation into lethally ablated recipients.

Animals↗
PubMed1985

Functional clonal deletion versus active suppression in transplantation tolerance induced by total-lymphoid irradiation.

Transplantation tolerance and stable chimerism were established in adult mice conditioned with a short course of total-lymphoid irradiation (TLI) followed by infusion of 30 X 10(6) allogeneic bone marrow cells. Spleen cells of tolerant mice could not exert a proliferative or cytotoxic response against host-type cells in vitro and were unable to induce graft-versus-host reaction in secondary host-type recipients. The degree of suppression assessed by coculturing tolerant splenocytes in vitro in the one-way mixed lymphocyte reaction was quite variable--and, in some cases, was not at all demonstrable, although tolerance was clearly maintained. Suppression, when apparent, could not be ascribed to T lymphocytes. Suppressor cells were found to bind soybean agglutinin and could be separated from the nonsuppressive cells by means of this lectin. Dissociation of the suppressive population (SBA+ cells) from that which is normally alloreactive (SBA- cells) resulted in a suppressor cell-depleted fraction that was still unable to respond to host-type cells but regained reactivity to unrelated cells. Limiting dilution analysis of chimeric splenocytes revealed markedly reduced frequencies of cytotoxic T lymphocyte precursors (CTL-P) directed against host-type cells, as compared with normal splenocytes reacting against the same target cells. This difference was accentuated when these cells were sensitized to host-type target cells prior to plating in limiting dilution cultures. In 1:1 mixing experiments of normal and chimeric splenocytes, there was no evidence of any in vitro suppressive activity to account for hyporeactivity of chimeric cells against host-type cells. Thus, maintenance of TLI-induced tolerance seemed not to be mediated primarily through an active suppressor cell mechanism.

Animals↗
PubMed1984

In vitro elicitation of cytotoxic response against a nonimmunogenic murine tumor by allosensitization.

The murine lymphoma (thymoma) PIR-2 of C57BL/6 origin, primarily induced in our laboratory by fractionated X-ray irradiation, has been shown to be nonimmunogenic by its failure to immunize syngeneic mice in vivo or to evoke a cytotoxic response in primary mixed lymphocyte-tumor cell cultures (MLTC) in vitro. We were able, however, to demonstrate the existence of anti-PIR-2 cytotoxic cells among allogeneic-primed C57BL/6 responding lymphocytes using the technique of limiting dilution cultures (LDC). The frequency of anti-PIR-2 cytotoxic cells among C57BL/6 lymphocytes sensitized against BALB/c splenocytes in mixed leukocyte culture (MLC) was 1/20 to 1/40, and the cytotoxic activity of positive LDC wells against PIR-2 reached 60% as determined by a 4-h 51Cr-release assay. The frequency of anti-PIR-2 cytotoxic cells could be increased two- to 10-fold (up to 1/4) by removing nylon-wool-adherent cells from the primed cell population and/or by enriching the primed lymphoblast population on a Percoll density gradient. Anti-PIR-2 cytotoxic cells were found to be Thy1+; Lyt1-2+ cells. Clones isolated from the LDC wells manifested strong cytotoxic activity toward PIR-2 cells and the stimulating BALB/c splenocytes but not against other H-2b tumor lines or C57BL/6 splenocytes. We suggest that the procedure of allostimulation in MLC-LDC is an effective in vitro means of generating highly reactive cytotoxic cells against poorly immunogenic neoplasms.

Animals↗
PubMed1980

Studies on the immune response to fixed antigens. IV. Recall of immunologic memory with fixed antigens.

The chemically modified antigens, trinitrophenylated sheep red blood cells (SRBC) and glutaraldehyde-SRBC, elicited specific secondary responses in mice but were unable to induce primary responses. They also induced specific immunologic memory. The secondary immune response was directed to the specific determinants of SRBC but not to new antigenic determinants created by the chemical modification process. The interpretation of these findings is discussed in relationship to the ability of fixed antigens to be processed by macrophages.

Animals↗
PubMed1978

Cellular assay for measuring anti-erythrocyte antibody responses.

Splenocytes from mice immunized with sheep red cells (SRC) or donkey red cells (DRC) were able to lyse radiolabeled SRC or DRC respectively. The cytotoxic effect was mediated by the active supernatant which was released from the immune splenocytes and which was characterized as antibody. This cellular cytotoxic response was found to be a very reliable, efficient, rapid and objective assay for measuring anti-erythrocyte antibody responses.

Animals↗
PubMed1978

Studies on the immune response to fixed antigens. III. Induction of helper function for antibody-dependent cellular cytotoxicity responses.

Heavy trinitrophenylated sheep red cells (TNP128SRC) and glutaraldehyde-treated SRC (G-SRC) could not induce cellular cytotoxicity against 51Cr-SRC. In contrast, the native antigen SRC could stimulate a cytolytic response against the radiolabeled homologous target cell. However, fixed SRC could stimulate a priming function that accelerated and augmented the secondary cytotoxic response to SRC. Such fixed antigens could stimulate a delayed-type hypersensitivity (DTHS) response also. Thus, the immunologic memory to the chemically modified antigen, as well as the DTHS response, are completely dissociated from the primary cytotoxic responses. The primary and the secondary cytotoxic responses that were developed in the spleens of the injected mice were mediated by antibody-dependent cellular cytotoxicity (ADCC), since the active supernatant that was released from the spleen cells could lyse the target cells in the presence of normal splenocytes. The active supernatant was identified as antibody. We suggest that B effector cells cytolyzed the antibody-coated target cells. Normal cells from nude mice could mediate the cytolytic process as efficiently as spleen cells from other strains of mouse. The results are discussed in terms of selective stimulation of T cell subpopulations.

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