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T Lea

Publications and source records attributed to T Lea.

69 records · Page 4Linked to original sources

Do OKT 3 monoclonal antibodies inhibit T-cell proliferation by blocking the receptor for TCGF?

OKT 3 monoclonal antibodies strongly inhibit the proliferation of T-cell growth factor (TCGF)-dependent continuously-growing T-lymphoblasts. The inhibition was shown to be dose-dependent reaching close to 70% in a concentration of 10 micrograms/ml. By using a purified radiolabelled TCGF preparation the inhibition was shown to take place at the level of growth factor binding. These results are consistent with OKT 3 monoclonal antibodies reacting with a membrane structure on or close to the TCGF receptor on activated human T-lymphocytes.

Antibodies, Monoclonal↗

In situ characterization of mononuclear cells in rheumatoid tissues, using monoclonal antibodies. No reduction of T8-positive cells or augmentation in T4-positive cells.

The reactivity of monoclonal mouse anti-human antibodies specific for mononuclear cell surface antigens were studied by the indirect immunofluorescence technique in frozen synovial tissue sections from patients with rheumatoid arthritis (RA). Most of the proliferating synovial lining cells were positive for HLA-DR antigens and monocyte-specific antigens, since they reacted with the OKIa1 and OKM1. Cells positive for HLA-DR and monocyte antigens were also seen scattered or in small nests in the synovial stroma, probably representing synovial cells or monocytes/macrophages. Some of the HLA-DR-positive cells may also be B lymphocytes or activated T cells. Endothelial cells were also HLA-DR antigen-positive. Monoclonal antibodies with specificity for all T cells (OKT3), for helper/inducer cells (OKT4), and for suppressor/cytotoxic cells (OKT8) reacted with cells often located in follicle-like structures around vessels. Cells with the T4 phenotype tended to be located in the centre of the follicles, whereas the T8 positive cells were more peripherally situated. In most instances fewer cells were positive for the T8 than for the T4 marker. In some instances there was as many T8-positive cells as T4-positive cells. Complete lack of T-lymphocyte subpopulations was not seen.

Animals↗

Quantitation of cells secreting immunoglobulins after elution from rheumatoid synovial tissue.

Mononuclear cells (MNC) eluted from rheumatoid synovial tissue of 16 patients with rheumatoid arthritis were examined for immunoglobulin-secreting cells (ISC). Immediately after elution and separation synovial tissue MNC contained considerable numbers of ISC. IgG and IgA ISC were more abundant than IgM ISC. At the same time there were low numbers of ISC in blood. Synovial tissue ISC were lost during incubation with pokeweek mitogen (PWM), possibly because tissue MNC were already maximally triggered in vivo. This was in contrast to blood MNC, in which the number of ISC increased significantly during incubation with PWM.

Antibody-Producing Cells↗

Demonstration of non-idiotypic variable heavy chain (VH) antigens on human peripheral blood lymphocytes.

In this study we have obtained evidence for the expression of Vh-like determinants on unstimulated human T lymphocytes as well as T lymphoblasts. These determinants were detected with antisera raised against isolated VH fragments of a human IgG3 cryoglobulin (KUP). The antisera detect idiotypic, VH subgroup and HV framework determinants and behave as anti-immunoglobulin antibodies when tested against peripheral blood mononuclear cells in immunofluorescence experiments. However, sensitive radiolabelling and immunoprecipitation techniques revealed a certain reactivity against highly purified T lymphocytes. The specificity of these T-cell-reactive antibodies has not been fully established, but the results suggest that the antisera contain antibodies directed at VH fragment-specific antigens or antigens not exposed on native immunoglobulins or isolated heavy chains.

Cell Separation↗

Anti-VH antibodies interfere with antigen binding by human T lymphocytes.

The effect of antisera against a VH fragment have been investigated in several T cell proliferative assay systems. Anti-VH antisera raised in sheep, rabbits and chicken induced profound inhibition of PPD stimulated lymphoproliferation. Likewise were both mixed lymphocyte reaction (MLR) and autologous mixed lymphocyte reaction (AMLR) severely hampered while stimulation induced by mitogens was only minimally affected. Specificity testing indicates that the inhibiting antibodies in these experiments are not directed against native immunoglobulin determinants but rather against determinants specific for the VH fragment. These results thus support the notion that T cells express VH antigens and that these antigens are part of or closely associated with the antigen receptor on human T lymphocytes.

Antibodies, Anti-Idiotypic↗

Sheep, rabbit and chicken antisera against a human VH fragment: reactivity with immunoglobulins and lymphocytes.

Antisera against a human VH fragment obtained from an IgG3, VH II, kappa protein (KUP) were raised in rabbits, sheep and chicken. The three types of anti-VH antisera reacted equally well with both intact immunoglobulin molecules and isolated heavy chains. The antisera did not detect any free heavy chain specific antigens by sensitive enzyme-linked immunosorbent assay (ELISA) tests although they reacted with some antigens which were more or less hidden on intact immunoglobulin molecules but well expressed on isolated heavy chains. The antisera reacted with more than 90% of IgG, IgA and IgM present in normal pooled serum. Experiments with T cells from normal peripheral blood indicated that the sheep and rabbit anti-VH antisera reacted with a 70,000 mol.wt T-cell surface antigen.

Animals↗

Characterization of the mitogenic and antigenic stimulatory properties of a purified streptolysin O preparation.

In vitro transformation of human peripheral blood lymphocytes was induced by a purified group A streptococcal extract rich in streptolysin O (SLO). The stimulation was shown to be largely a general mitogenic effect rather than antigen-selective as a large panel of normal blood donors responded strongly. Further support for a non-specific stimulation was obtained by experiments with cord blood lymphocytes. An antigen-specific response could also be detected as culture supernatants from the stimulation experiments contained immunoglobulins with SLO neutralizing properties. In addition, the total response could partly be inhibited by rabbit heteroantisera against HLA-DR-like antigens supporting the above contention. The stimulatory properties were found to reside in the SLO molecule although results may indicate that the determinants provoking the lymphocyte transformation differ from the determinants possessing the haemolytic properties. Peak response was found on days 4-5. Cell fractionation experiments indicated that only T lymphocytes were stimulated although co-operating B cells and/or monocytes were necessary.

Antibodies↗

Unique antigenic determinants (idiotypes) used as markers in a patient with macroglobulinemia and urticaria. Similar idiotypes demonstrated in the skin and on peripheral blood lymphocytes.

An antiserum was raised against a monoclonal IgMk macroglobulin isolated from serum of a patient with recurrent urticaria. The antiserum was made idiotype-specific through adequate absorptions. The anti-idiotype antiserum reacted only with the immunizing protein and its Fab fragments and not with other monoclonal proteins of IgM and IgA class or pooled IgG as assayed in an enzyme-linked immunosorbent assay. IgM antibodies with the same idiotype as the monoclonal IgM protein were detected in the dermal/epidermal junction area of diseased skin. The similar idiotypic determinants could also be demonstrated on membrane-bound molecules of peripheral blood B and T lymphocytes using the immunofluorescence methods.

Electrophoresis, Agar Gel↗

Shared idiotypes of human peripheral blood B and T lymphocytes.

In a patient with an IgG lambda monoclonal serum component possessing anti-streptolysin O activity, we have demonstrated peripheral blood B and T lymphocytes with shared or similar idiotypes. The idiotypic T lymphocyte membrane structure was capable of binding the specific antigen (SLO). After radioiodination and subsequent detergent solubilization of the same T cell population, immunoprecipitation of the lysate by employing anti-idiotypic antibodies, resulted in the isolation of a polypeptide chain with a m.w. of 70,000 on SDS polyacrylamide gels under reducing conditions. The polypeptide expressed no isotypic immunoglobulin markers. Internal labeling experiments indicated that this membrane structure was actively synthesized by the T lymphocytes.

Antigens↗

Carbamazepine: effect on IgG subclasses in epileptic patients.

IgG subclass concentrations were determined in sera from 20 epileptic patients before carbamazepine therapy and after 6 weeks of treatment. Subclass-specific monoclonal antibodies were used in an ELISA technique. Carbamazepine reduced the IgG2 concentration in 13 patients, and the mean value fell from 3.21 to 2.47 g/L during the carbamazepine treatment (p less than 0.01). This IgG2 decrease was maintained after 4 and 12 months of carbamazepine therapy. IgG1, IgG3, and IgG4 concentrations did not change. IgG2 deficiency was not seen. The reduction in IgG2 was not related to the carbamazepine serum concentration within the therapeutic range, to the type of epilepsy, or to the age of the patient. The carbamazepine-induced reduction of IgG2 in serum may indicate an altered immune response to certain antigens, preferentially to carbohydrates.

Adolescent↗