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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 271 records · Page 15Linked to original sources
PubMed1983

Resting and activation antigens of T cells: studies with OKT10 and OKT20 monoclonal antibodies.

OKT10 and OKT20 are monoclonal antibodies that recognize cell surface antigen(s) on resting thymocytes, plasma cells, null cells, monocytes, and some bone marrow cells. The respective antigens, poorly expressed on resting peripheral T cells, are strongly expressed on T cells activated either in vitro or in vivo. Double-staining experiments using either OKT10 or OKT20, in combination with OKT3, provided paradoxical results. If indirect staining with OKT3 plus horse alpha-mouse IgG preceded staining with OKT10 or OKT20, most cells showed double staining; all other staining sequences yielded the expected result that OKT3+ cells expressed very little OKT10 or OKT20. Analysis of the experiments revealed that perturbation of the cell membrane with a monoclonal antibody reactive with a cell surface antigen (for example, OKT3) followed by a crosslinking second antibody caused the expression of these antigens. This suggests that these antigens, normally expressed on activated T cells, are actually present in an unexpressed form within the membrane of resting T cells.

Animals↗
PubMed1983

Monitoring immunosuppression following renal transplantation.

Renal allograft recipients were given azathioprine and prednisone for immunosuppression following transplantation. In addition, pulses of steroids or courses of treatment with antithymocyte globulin (ATG) or PAN.OKT3 were employed to combat acute rejection episodes. Our results support the concept that ATG and PAN.OKT3 are useful in the treatment of acute kidney allograft rejection. In our experience, ATG often reversed acute kidney allograft rejection episodes and then provided relatively long-lasting immunosuppression with stable graft function. In contrast, PAN.OKT3 was more effective in reversing acute rejection, but subsequent rejection episodes occurred more frequently. In patients treated with PAN.OKT3, cells reacting with OKT3, OKT4 and OKT8 were removed from the circulation within minutes following the initial treatment, and the levels of these cells remained dramatically depressed during the first few days of treatment. Subsequently, peripheral blood cells which reacted with OKT4 or OKT8, but not OKT3, could be detected in most patients, even though treatment continued and excess circulating PAN.-OKT3 was present. Experiments in which these cells were cultured for 24 or 72 hr indicated that antigenic modulation by OKT3 had occurred in vivo. These results raise interesting questions about the mode of action of PAN.OKT3, and suggest that the combination of PAN.OKT3 with an agent which can establish long-lasting immunosuppression may be more effective than either agent given alone.

Antibodies, Monoclonal↗
PubMed1983

Generation and characterization of monoclonal antibodies reactive with human B lymphocytes.

Four novel monoclonal antibodies directed at determinants on human B lymphocytes were produced and characterized by flow cytometry using indirect immunofluorescence analysis. The antibodies, OKB1, OKB2, OKB4, and OKB7, define antigens not previously described on human B lymphocytes using B cell reactive monoclonal antibodies or standard B cell phenotypic markers. OKB4 [immunoglobulin M (IgM)] and OKB7 (IgG2a) were reactive with greater than 95% of all surface membrane immunoglobulin positive (Smlg+) lymphocytes and were restricted to the B cell lineage. OKB2 (IgG1) likewise reacted with greater than 95% of all Smlg+ lymphocytes; however, the antigen was also expressed on all granulocytes. In contrast to OKB2, OKB4, and OKB7, OKB1 reacted with a variable percentage of normal peripheral B cells (approximately 70 to 95%). Functional studies employing polyclonally activated B cells in a pokeweed mitogen (PWM) driven system and the reverse hemolytic plaque assay for the quantitation of Ig secreting plasma cells demonstrated that OKB1 and OKB2 inhibited the generation of plaque-forming cells (PFC) when added to cultures at day 0. OKB4 had a marginal inhibitory effect, whereas OKB7 consistently enhanced the PFC response. Immunoprecipitation studies with OKB1, OKB4, and OKB7 demonstrated that these antibodies precipitated antigens of approximately 168,000, 87,000, and 175,000 m.w., respectively. The OKB2 antigen is presently under study.

Animals↗
PubMed1983

Alcoholic seizures: intellectual and neuropsychological sequelae.

Alcoholics who experienced withdrawal seizures performed comparably to those who did not suffer seizures on intellectual and neuropsychological tests. Both groups, however, exhibited a number of impairments. The hypothesis that the withdrawal seizure is indicative of alcoholism severity and can serve as a marker for extent of neurological disturbance was not supported.

Alcoholism↗
PubMed1982

T cell development in normal and thymopentin-treated nude mice.

The extent and diversity of T cell differentiation in nude athymic mice are matters of dispute. In this study, we examined the splenic T cell population of pathogen-free and germ-free nu/nu mice, treated or not treated with the pentapeptide analogue of thymopoietin (TP-5), in terms of TL, Qa-1, and Lyt phenotypes. At all ages, 50-60% of nu/nu splenocytes, enriched for T lymphocytes by removal of sIg+ cells, expressed T markers, as compared with greater than 85% in normal mice. At 2 mo of age, all nu/nu splenic T cells expressed the surface phenotype TL+:Thy-1+:Ly-123. This is abnormal in two respects: first, because expression of TL is normally confined to thymocytes; and second, because there was no evidence of the usual diversification into the subsets Ly-1 and Ly-23. From 10 wk of age onwards, diversification into Ly subsets was evident in nu/nu spleen, although the usual predominance of Ly-1 over Ly-123 cells was not attained, and some TL+ cells persisted. Also, the ratio of Qa-1+ to Qa-1- cells rose progressively to as high as 4:1 at 4-6 mo, in contrast to the usual ratio of approximately 1:1, regardless of age. In the spleens of nu/nu mice treated with TP-5 from 5-8 weeks of age and tested 1 wk later, the proportion of T cells was raised, though not to normal levels, the number of TL+ cells was reduced, and there was diversification into Ly sets.

Age Factors↗
PubMed1982

Possible involvement of the OKT4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of cytotoxic T lymphocytes specific for SB antigens.

A recently described HLA gene, SB, which maps between GLO and HLA-DR, codes for Ia-like molecules that are similar to but distinct from HLA-DR molecules. Cytotoxic T lymphocytes (CTL) specific for SB1, SB2, SB3, and SB4 were compared with HLA-A2-specific CTL with respect to their surface expression of the T cell differentiation antigens OKT3, OKT4, and OKT8. All CTL activity was eliminated by treatment with OKT3 and C'. The SB-specific cytotoxicity was eliminated by OKT4 plus C' but not by OKT8 plus C'. In contrast, HLA-A2-specific killing was completely susceptible to treatment with OKT8 plus C' but not with OKT4 plus C'. Cytotoxicity was analyzed in the presence of OKT8 and a series of monoclonal antibodies (OKT4A, 4B, 4C, and 4D) that react with distinct epitopes on the OKT4 molecule. SB1-, SB3-, and SB4-specific CTL were partially inhibited by OKT4A and 4B (45-75%), whereas HLA-A2-specific CTL were partially inhibited by OKT8 (48-63%) but not by OKT4. SB2-specific CTL were not inhibited (less than 26%) by OKT8 or by any of the OKT4-related antibodies. These results suggest that the OKT4 marker may be expressed on most T cells that recognize allogeneic Ia or self Ia plus foreign antigens; OKT4+ cells do not appear to be functionally homogeneous in that they can act both as helper/inducer and cytotoxic cells. Models are proposed for the functional involvement of the OKT4 molecule in T cell-Ia antigen interactions.

Antibodies, Monoclonal↗
PubMed1982

Pretreatment of donor bone marrow with monoclonal antibody OKT3 for prevention of acute graft-versus-host disease in allogeneic histocompatible bone-marrow transplantation.

Ten consecutive patients undergoing transplantation of bone marrow from histocompatible siblings for treatment of haematological malignancy took part in a pilot study to test the safety of in-vitro treatment of donor bone marrow with monoclonal antibody OKT3. Three male and seven female patients aged 7-34 years received concentrated bone marrow buffy-coat cells which had been incubated with OKT3 before infusion. In-vitro studies confirmed that almost all immunocompetent T lymphocytes in the bone-marrow samples were coated with OKT3 at the time of infusion. In vitro, neonatal rabbit complement inhibited the proliferation of bone-marrow T lymphocytes in samples preincubated with OKT3 to less than 4% of the mitogenic responses of the untreated bone marrow. In contrast, fresh autologous complement did not effectively lyse OKT3-treated bone-marrow cells. Infusion of OKT3-treated bone marrow was safely accomplished, and engraftment was achieved in all patients (mean 23 days). Nine of ten patients survived for more than 100 days after bone-marrow transplantation, but significant acute graft-versus-host disease (GvHD) requiring treatment with steroids developed in five of the ten. This finding suggests that further modifications for bone-marrow pretreatment will be needed to achieve effective prophylaxis against acute GvHD in histocompatible bone-marrow transplantation.

Acute Disease↗
PubMed1982

[In vivo induction of antigenic modulation in man by an anti-T cell monoclonal antibody (author's transl)].

The anti-T cell monoclonal antibody OKT3 was administered to renal allograft recipients. A dramatic depletion of peripheral T cells was immediately observed followed, after 2-5 days, by the reappearance of a limited but significant number of or OKT3-4+ or OKT3-8+T cells showing antigenic modulation of the OKT3-defined antigen. These cells recovered the OKT3 receptor after overnight in vitro incubation.

Antibodies, Monoclonal↗
PubMed1982

Use of anti-T-cell monoclonal antibody OKT3 to prevent acute graft-versus-host disease in allogeneic bone-marrow transplantation for acute leukaemia.

Seventeen patients who received allogeneic bone-marrow transplants from matched or slightly mismatched (in four patients) siblings were observed for at least 60 days or until acute graft-versus-host disease (GvHD) developed. All donor marrows after preliminary manipulation were incubated with 1 mg of the murine monoclonal antibody OKT3 before infusion in an attempt to deplete them of immunocompetent T lymphocytes (opsonisation). In three of the seventeen patients acute GvHD of grade II or greater developed. Two of these patients died, but they had disseminated cytomegalovirus infection as well as GvHD. Eleven patients showed no evidence of acute GvHD, and four had transient limited skin rashes (grade I GvHD). Opsonisation of T lymphocytes has reduced the incidence of severe acute GvHD in this unit from 79% in an earlier group of 14 patients to 18% when added to prophylactic methotrexate.

Acute Disease↗
PubMed1982

Modulation of T leukaemic cell phenotype with phorbol ester.

A panel of monoclonal antibodies and other markers (e.g., terminal deoxynucleotidyl transferase, sheep erythrocyte rosettes, peanut agglutinin) have been used in conjunction with flow cytometry and biochemical analysis to monitor the induction of maturation in human thymic (T) leukaemic cell lines by phorbol ester (TPA). Seven cell lines underwent multiple phenotypic alterations in response to TPA but were unresponsive to synthetic thymic hormones (TP5, FTS) or to other compounds (e.g. DMSO, retinoic acid) which induce maturation in other types of leukaemia. The changes parallel those observed in normal T-cell differentiation and partly reflect alterations in glycosyl transferase activity, altered synthesis of proteins and regulation of cell surface receptors (for transferrin) associated with rapid growth and metabolism. These studies further illustrate the reversibility of maturation arrest in human leukaemia and provide support for the view that leukaemia may involve regulatory defects in the coupling of proliferation and maturation. Induction of promotion of terminal differentiation in leukaemic equivalents of T-cell precursors may provide a convenient system for the study of biochemical and molecular events involved in T-cell development and diversification.

Antibodies, Monoclonal↗
PubMed1982

Monoclonal antibodies OKT 11 and OKT 11A have pan-T reactivity and block sheep erythrocyte "receptors".

Monoclonal antibodies OKT11 (gamma 1) and OKT11A (gamma 2) are described and appear to have similar binding specificities. They bind, in immunofluorescence, with greater than 95% of infant thymocytes, staining both cortical and medullary cells, 65-80% of blood lymphocytes and selectively stain the T cell-dependent paracortical areas of tonsil. A small proportion (9-12%) of bone marrow lymphocytes stain, but this population excludes the terminal transferase-positive cells. Both the gamma 1 and gamma 2 antibodies stain the surface membrane Ig-negative lymphocytes in blood and tonsil and are to block sheep E rosette formation (to normal or leukemic T cells). In contrast, other monoclonal anti-T reagents tested (OKT1, OKT3, OKT4, OKT6, OKT8, OKT9, OKT10) did not block E rosette formation. E rosette formation and OKT11 bindings are coincident on T-ALL cell lines and both are trypsin-sensitive. In a series of 145 leukemias and 26 leukemic cell lines investigated, only leukemias with a T cell phenotype including E rosette positivity were reactive with OKT11 and OKT11A. OKT11A binds to a polypeptide of approximately 50 000 molecular weight on thymic lymphocytes. This structure may carry the recognition site for sheep erythrocytes. These antibodies provide additional useful markers for T cell analysis and are of potential therapeutic value.

Animals↗