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Y Reisner

Publications and source records attributed to Y Reisner.

At least 91 records · Page 5Linked to original sources
PubMed1986

Changes in sialyltransferase activity during murine T cell differentiation.

The main aim of our study was to investigate whether the marked decrease in the expression of peanut agglutinin (PNA) receptors during T-cell maturation in the mouse is accompanied by increased activity of sialyltransferase. By differential agglutination with PNA, mature thymocytes (PNA-) were separated from immature ones (PNA+) and the separated fractions were tested for their sialyltransferase activity with asialofetuin as acceptor. In parallel, sialyltransferase activities of hydrocortisone-resistant thymocytes and untreated thymocytes were also compared. Optimization of the enzyme assay revealed that previous results in the literature were obtained under suboptimal conditions. Using manganese chloride instead of magnesium chloride, we have now found that hydrocortisone-resistant thymocytes contain 3.3-fold more sialyltransferase activity compared to untreated thymocytes. PNA- thymocytes contain 8.1-fold more enzyme activity compared to the PNA+ cells. Studies with fluorescein conjugated PNA of the agglutinated and unagglutinated thymocyte fractions suggest that the trace amount of sialyltransferase activity found in the PNA+ fraction may result from 5 to 10% cross-contamination with PNA- cells. These results suggest that the cellular levels of sialyltransferase specific for asialofetuin may play an important role in T-cell differentiation.

Animals↗
PubMed1986

Demonstration of clonable alloreactive host T cells in a primate model for bone marrow transplantation.

The phenomenon of marrow rejection following supralethal radiochemotherapy was explained in the past mainly by non-T-cell mechanisms known to be resistant to high-dose irradiation. In the present study a low but significant number of radiochemoresistant-clonable T cells was found in the peripheral blood and spleen of Rhesus monkeys following the cytoreductive protocol used for treatment of leukemia patients prior to bone marrow transplantation. More than 95% of the clonable cells are concentrated in the spleen 5 days after transplant. The cells possess immune memory as demonstrated by the generation of alloreactive-specific cytotoxicity. The present findings suggest that host-versus-graft activity may be mediated by alloreactive T cells. It is hoped that elimination of such cells prior to bone marrow transplantation will increase the engraftment rate of HLA-nonidentical marrow in leukemia patients.

Animals↗
PubMed1986

Evaluation of HLA-haplotype disparate parental marrow grafts depleted of T lymphocytes by differential agglutination with a soybean lectin and E-rosette depletion for the treatment of severe combined immunodeficiency.

The factors that impact upon successful bone marrow transplantation leading to immunologic reconstitution in severe combined immune deficiency (SCID). Wiskott-Aldrich syndrome, and in other lethal congenital immunodeficiencies are reviewed. Evidence is presented that graft-versus-host disease (GVHD) can be abrogated by the depletion of T cells, even from histoincompatible marrow grafts. However, graft resistance or restricted immune reconstitution has been observed with significant frequency. The bases for T cell reconstitution and limitations in B cell humoral immune recovery in the postgrafting period are reviewed, together with emerging evidence that pretransplant cytoreduction might obviate some of these problems.

Agglutination Tests↗
PubMed1985

Differential binding of soybean agglutinin to human neuroblastoma cell lines: potential application to autologous bone marrow transplantation.

Normal human bone marrow cells were mixed with neuroblastoma cells from four different human cell lines, and the cell mixtures were separated by differential agglutination with soybean agglutinin (SBA). The unagglutinated cell fraction, previously shown to be highly enriched for the hematopoietic pluripotential stem cells and capable of reconstituting lethally irradiated adult patients with acute leukemia, was further fractionated by affinity chromatography on the lectin conjugated to Sepharose 6MB beads. Two independent assays, one using radiolabeling of the tumor cells and the other based on cloning of the neuroblastoma cells on agar, showed that the agglutination step alone removes 64-76% of the radiolabeled neuroblastoma cells and 85-98% of the clonogenic cells from the tumor/bone marrow cell mixture. Passage of the unagglutinated radiolabeled cells through SBA-Sepharose columns results in further purging of 28-53% of the neuroblastoma cells. Thus a combination of the two methods affords only one-log depletion for the neuroblastoma cells, compared to a three-log depletion achieved for a T-cell leukemia line CEM tested in parallel. It seems therefore that the agglutination technique, or the use of SBA-Sepharose columns, can be used only as a preliminary step for the purging of neuroblastoma cells from involved human bone marrow preparations. Staining with fluorescein isothiocyanate-conjugated SBA of nine different neuroblastoma cell lines, including the four tested in the fractionation studies, showed that more than 98% of the cells, of all the cell lines tested, specifically bind to the lectin, whereas no specific binding can be detected on the stem cell-enriched bone marrow cell fraction. However, the total number of receptors on the neuroblastoma cells is small compared to that of line CEM or normal granulocytes, which are strongly agglutinated by SBA. It seems therefore that the quantitative difference in the total number of SBA receptors is a crucial factor for purging by the agglutination technique or by affinity chromatography. Although these results show limitations to the use of both methods, this study establishes that all neuroblastoma cell lines tested express receptors for the lectin. Improved purging of neuroblastoma cells may possibly be achieved by targeting SBA-bound toxins or magnetic spheres to these receptors.

Agglutination↗
PubMed1985

B-cell function in common variable immunodeficiency: suppression of in vitro anti-sheep erythrocytes antibody production by T cells and monocytes.

Peripheral blood mononuclear (PBM) cells from five of 21 patients with common variable immunodeficiency (CVI) stimulated in vitro by antigen produced antibodies normally. In 11 of the 16 non-responders, removal of adherent suppressor cells by Sephadex G-10 or removal of monocytes or OKT8 positive suppressor lymphocytes by other means of separation made antibody responses demonstrable. Cells adherent to the G-10 column had suppressor function in the autologous antigen driven system; the suppressor activity appeared to be due to adherent T cells in some patients and to adherent monocytes in others. The suppressor cell functions in these patients did not correlate significantly with the number of cells positive for monoclonal antibodies OKT8 or Leu-2. Factors suppressing antibody production in this system were found in normal serum but usually not in serum of the patients with CVI studied. Substances in normal serum which enhance antibody production in this system when added late in culture were present in serum of patients with CVI. Any abnormality of interleukin-1 production by monocytes of these patients did not seem relevant to the immunodeficiency.

Adolescent↗
PubMed1984

Immunoreconstitution in severe combined immunodeficiency after transplantation of HLA-haploidentical, T-cell-depleted bone marrow.

Immunological reconstitution by transplantation of HLA-haploidentical, paternal bone marrow was attempted in four infants with severe combined immunodeficiency who lacked HLA-identical donors. To prevent graft-versus-host disease, T lymphocytes were removed from the grafts by agglutination with soybean agglutinin and rosette formation with sheep red blood cells. None of the patients received conditioning treatment before transplantation. Normal, donor-derived cellular immune functions developed in all four patients within several months of transplantation. Threatening complications of graft-versus-host reactions were not seen. All four patients remain in excellent health 12-15 months after discharge home, with persisting normal T-cell functions.

Bone Marrow↗
PubMed1983

Bone marrow transplantation--an expanding approach to treatment of many diseases.

Thus, we can conclude that marrow transplantation has already influenced medical practice greatly. It has offered a treatment which often cures patients of more than 20 otherwise lethal diseases. The treatment so horrendously difficult and dangerous at first has already been greatly improved, simplified, and made much safer. The availability of a suitable donor has been much extended and real progress has been made in prevention and perhaps even in treatment of graft-versus-host disease. This has made possible the option of marrow transplantation for every patient in whom we think the treatment may be beneficial. The problem underlying many cases of interstitial pneumonia has been identified and patients are already benefitting clinically from this progress. Progress has also been made which promises antiviral therapy which could reduce, prevent, and ultimately eliminate the intercurrent virus infections which limit the applicability of marrow transplantation, especially for children with severe immunodeficiencies. I do not know how far this line of investigation can be taken. However, just as we have learned stepwise to use marrow transplants from matched siblings to treat many diseases, to use fetal liver in place of bone marrow, to employ matched relative donors when a matched sibling is not available, and, finally, even to use parental donors to achieve correction of SCID, we now have good reason to believe that, ultimately, we can use marrow transplantation without fear of GVHD to address many additional genetically determined and acquired diseases; certainly, for those diseases that involve any of the cells that are derived from bone marrow cells, and perhaps for those attributable even to cells of other organs and tissues, the functions of which are, in whole or in part, a consequence of interactions of marrow-derived cells and cells of ectodermal or endodermal origin, marrow transplantation may be useful. To us, the future of marrow transplantation as a major modality of treatment or prevention of many diseases, including hemoglobinopathesis, immunodeficiencies, hematologic abnormalities, abnormalities of function of marrow-derived cells, and even inborn errors of function of cells of organs and tissues not of marrow origin, seems bright, indeed. Further, with the capacity to introduce resistance genes against viruses and malignancies, autoimmune diseases, and diseases dependent on anomalies of immune response genes, marrow transplantation for many other diseases seems a more remote possibility.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Deaminase↗
PubMed1983

Differential agglutination by soybean agglutinin of human leukemia and neuroblastoma cell lines: potential application to autologous bone marrow transplantation.

Normal human bone marrow cells were mixed with radioactively labeled tumor cells from different leukemia and neuroblastoma cell lines, and the cell mixtures were separated by differential agglutination with soybean agglutinin. It is shown that the cell fraction unagglutinated by soybean agglutinin, which was previously found to be capable of reconstituting the hematopoietic system of lethally irradiated recipients, can be purged of tumor cells with varying efficiency depending on the tumor cell expression of soybean agglutinin receptors as detected by flow cytofluorimetry with fluoresceinated soybean agglutinin.

Animals↗
PubMed1983

Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells.

Three patients with severe combined immunodeficiency (SCID) received transplants of HLA haplotype-mismatched parental bone marrow depleted of T lymphocytes by differential agglutination with soybean agglutinin (SBA) and subsequent E-rosette depletion. Two patients achieved durable engraftment with reconstitution of both humoral and cell-mediated immunity. Neither of these patients developed graft versus host disease (GVHD). The third patient achieved only a transient engraftment with concomitant development of mitogen-responsive lymphocytes of paternal origin. Our experience indicates that depletion of T lymphocytes by this technique can abrogate the potential of histoincompatible marrow grafts to induce lethal GVHD without limiting immunologic reconstitution. It also provides further evidence of nonimmune mechanisms of graft resistance that may necessitate preparative treatment of patients with SCID before transplantation with HLA-mismatched marrow cells.

Bone Marrow Transplantation↗
PubMed1982

Enrichment for CFU-C from murine and human bone marrow using soybean agglutinin.

Mouse bone marrow and spleen cells agglutinated by soybean agglutinin (SBA) or peanut agglutinin (PNA) were previously shown to be enriched for spleen colony-forming cells (CFU-S) and sufficiently depleted of graft-versus-host reaction producing cells to allow hematologic reconstitution of lethally irradiated allogeneic recipient mice. A similar enrichment for cells capable of forming colonies in soft agar culture (CFU-C) has now been found in the SBA-agglutinated fraction of mouse bone marrow cells, in contrast to the finding that in human bone marrow the majority of the CFU-C are in the fraction not agglutinated by SBA. Cytofluorometric studies with fluorescein-labeled SBA (FITC-SBA) revealed that the majority of both mouse and human bone marrow cells bind the lectin. Experiments mixing the human marrow fractions separated by SBA reveal that true enrichment for CFU-C is achieved in the unagglutinated fraction, as opposed to a possible depletion of a suppressor cell population. Granulocytic, monocytic, and mixed cell colonies were all enriched in the SBA-unagglutinated cell fraction from human bone marrow.

Animals↗
PubMed1981

Transplantation for acute leukaemia with HLA-A and B nonidentical parental marrow cells fractionated with soybean agglutinin and sheep red blood cells.

A new procedure for enrichment of marrow precursors and removal of T lymphocytes from large volumes of human bone marrow, involving initial differential agglutination of T lymphocytes and mature marrow elements with soybean agglutinin, followed by rosetting with sheep red blood cells, was used to fractionate marrow cells from an HLA-A, B, DR non-identical, MLC non-reactive, paternal donor for transplantation into an infant with acute leukaemia. This transplant became completely engrafted and resulted in full recovery of normal, donor-derived haematopoietic function without graft-versus-host disease, sustained for 11 weeks after transplantation, at which time the patient's leukaemia recurred. Subsequently, the patient received chemotherapy and achieved a remission with regeneration of normal marrow cells of donor origin. The patient's course demonstrated the potential of lectin-separated marrow grafts to restore durable haematopoiesis, without graft versus host disease, in a lethally irradiated allogeneic host.

Agglutinins↗
PubMed1980

Separation of antibody helper and antibody suppressor human T cells by using soybean agglutinin.

Soybean agglutinin (SBA) binds specifically to mouse B cells and has been used in the past to separate mouse B and T spleen cells by differential agglutination of the B cells. In the present study it was found that a major T-cell subpopulation of human peripheral blood mononuclear cells is agglutinated by SBA along with the B cells and monocytes. Tests of such cell surface markers as Fc receptors for IgG and IgM, as well as functional assays of antibody production by B cells, revealed that the SBA-agglutinated cell fraction contains the antibody helper T cells whereas the unagglutinated fraction is enriched with antibody suppressor T cells. Similar observations were made in tests of the proliferative response to mumps antigen. A recently prepared monoclonal antibody, anti-Leu 2a, which recognized the same thymus-dependent antigen previously defined by a heterologous anti-human T cell serum (alpha TH2), was found to define by indirect immunofluorescence a subpopulation of SBA- cells of intermediate staining intensity which was not detectable in the SBA+ population.

Antibody Formation↗