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Biomedical subjects

I M Roitt

Publications and source records attributed to I M Roitt.

At least 91 records · Page 5Linked to original sources
PubMed1983

Cell-surface changes during mitogenic stimulation of lymphocytes assessed by the binding of wheat-germ agglutinin and other plant lectins.

Lymphocytes from murine lymph node, cultured in the presence of an optimally mitogenic dose of phytohaemagglutinin, were stained with fluoresceinated lectins and analysed by flow cytometry. A marked increase in the ability of lymphocytes to bind wheat-germ agglutinin was observed that is particularly pronounced for the blast cells, reaching a maximum at about 40 h, when they are 5.5-times brighter than cells at zero time. The corresponding intensification of the small cells is 2-fold. Much smaller increases in binding accompanying blast transformation were observed when fluoresceinated concanavalin A or Lens culinaris haemagglutinin were used. Polyacrylamide gel electrophoresis of plasma membranes followed by treatment of the gels with radioactively labelled lectins and autoradiography also showed a very distinct increase in the binding of wheat-germ agglutinin to membranes from mitogen-stimulated porcine lymphocytes. Less marked changes in the binding of concanavalin A, Lens culinaris heamagglutinin and Ricinus communis agglutinin 120 were also noted. The apparent multiplicity of glycoproteins that bind each lectin, suggests that in each case the sites are heterogeneous. We conclude that lymphocytes stimulated by the T-cell mitogen phytohaemagglutinin expose new glycoprotein receptors for wheat-germ agglutinin that are most abundant on blast cells at 40 h. Attempts to characterize the receptor biochemically suggest that the carbohydrate moiety recognised by wheat-germ agglutinin is present on a glycoprotein of approx. 120 kDa molecular mass and also possibly on glycoproteins of 170-190 kDa.

Animals↗
PubMed1983

Functional evaluation of murine allogeneic T lymphoblasts separated by Vicia villosa lectin positivity.

Mixed-lymphocyte culture-stimulated cells have been fractionated by their ability to bind the lectin Vicia villosa (Vv) and assessed for their cytolytic and suppressor activity in vitro. Vv positive and negative cells were separated either by cell affinity chromatography using Vv-Sepharose 6MB chromatography or by electronic cell sorting with FITC-Vv. Both populations expressed marked cytolytic and suppressor cell activity. Thus this lectin cannot be used to discriminate between these and other functional lymphoid cell population of blastoid cells binding the FITC-Vv appears following allogeneic stimulation; treatment with the immunosuppressive drug cyclosporin A, which affects cytotoxic cells preferentially, results in a considerable reduction of the Vv positive blastoid cells.

Animals↗
PubMed1983

Anti-globulins and circulating complexes in early rheumatoid arthritis.

The importance of immunological parameters such as anti-globulins, anti-RANA and circulating immune complexes in rheumatoid arthritis (RA) has been studied by examining patients with early disease who are attending general practitioner clinics with joint pains for the first time. Anti-RANA, and IgG and IgM anti-globulins were detectable in the serum at the earliest time we were able to examine the patients. The anti-globulins had specificity for both rabbit and human IgG from the outset. Immune complexes were similarly raised in early disease. From these patients with early joint pains we were able to predict, by means of multivariant discriminant analysis of the laboratory data obtained from the first serum sample, between those who would develop into patients with classical or definite RA at 1 year and those who would have non-inflammatory joint disease.

Antibodies, Anti-Idiotypic↗
PubMed1982

The role of self-antigen in the development of autoimmunity in Obese strain chickens with spontaneous autoallergic thyroiditis.

Neonatal thyroidectomy of Obese strain (OS) chickens showed that the spontaneous development of thyroid autoimmunity in these animals was fully dependent upon the presence of autoantigen, and could not be ascribed essentially to antigen-independent mechanisms such as polyclonal lymphocyte activation or innate distortions within the idiotype network. Similarly, removal of the gland in animals with established thyroiditis demonstrated the need for antigen to maintain the autoimmune response. Thyroglobulin from normal chickens induced autoantibodies in neonatally thyroidectomized OS birds, suggesting that an abnormality in the structure of this protein is not a prerequisite for the development of autoimmunity. This contention is supported by the finding that OS and normal thyroglobulin were immunochemically indistinguishable, whether compared using OS autoantibodies or rabbit anti-chicken thyroglobulin sera.

Aging↗
PubMed1982

The immunological basis of autoimmune disease.

Organ-specific diseases often involve cell surface antigens which when functionally characterized prove to have some receptor function. Certain restricted parts of the molecule are autoantigenic but the response to these epitopes is similar to that provoked by foreign antigens with respect to diversity of class, clonality and probably idiotypy. The mechanisms controlling the response to components on the surface of the body's cells are not fully understood but might be circumvented by polyclonal activators or by the development of T suppressor dysfunction. The latter could occur through a generalized defect in T suppressor cells, which would account for the association of autoimmune diseases in given individual subjects. Alternatively, or in addition (since genetic studies suggest multifactorial influences), the suppressor defect could be antigen specific. Our studies in chickens with spontaneous autoimmune thyroiditis show that normal antigen is obligatory for both the development and maintenance of autoantibody production and that it is possible that some abnormality or change in the presentation of the autoantigen (rather than its structure) is concerned in the initiation process.

Aging↗
PubMed1982

Direct staining of mouse T lymphoblasts with fluoresceinated Vicia villosa lectin.

Fluorescein conjugated Vicia villosa (Vv) lectin was used for direct staining of the surface of viable cells of various mouse lymphocyte populations. A varying proportion of polyclonally-activated T cells expressed Vv receptor although less strongly than cells of an influenza virus-specific cytotoxic T lymphocyte (CTL) clone and blasts generated in the mixed lymphocyte reaction. Cyclosporin A (CyA) treatment markedly reduced the expression of Vv receptor following concanavalin A (Con A) stimulation by between 66% and 93% with a concurrent inhibition of blastogenesis and complete abrogation of cytolytic function. Resting mouse lymphocytes and B-cell blasts were always Vv-negative. However, non-specific suppressor factor producing non-cytotoxic T-cell lines also expressed Vv receptor as shown by the weak, but specific, surface fluorescence of EL4 and BW5147 cells stained with Vv. Vv-positive cells were not restricted to a particular Ly phenotype, Vv-positive cells being found among both Lyt 1+ and Lyt2+ MLC stimulated lymphocytes. Our data suggest that the receptor for Vv lectin cannot be regarded as an exclusive differential marker for CTL.

Animals↗
PubMed1982

Predisposition to organ-specific autoimmunity in Obese strain (OS) chickens: reactivity to thyroid, gastric, adrenal and pancreatic cytoplasmic antigens.

In addition to thyroglobulin autoantibodies, some Obese strain (OS) chickens gave organ-specific reactions with the cytoplasm of thyroid acinar cells when the sera were tested by immunofluorescence. The staining pattern was similar to that seen with human antibodies to thyroid microsomes. A proportion stained the proventricular glands of the chicken stomach in a manner indistinguishable from that of pernicious anaemia sera containing parietal cell antibodies. Isolated examples of organ-specific reactions with adrenal and exocrine pancreas were also recorded. These findings strengthen the notion that the OS chicken represents an authentic model for human organ-specific autoimmune disease. The high incidence of non-organ specific reactions complicates but does not necessarily invalidate this view since normal chickens show a propensity to develop such antibodies. However the OS chicken appears to differ from the human in being hyper-responsive to antigens in general.

Adrenal Glands↗
PubMed1982

Apparent failure of thymic epithelium transplants to alter the course of autoimmune disease in NZB/W mice.

Thymic epithelium from neonatal DBA/2 mice (H-2d) was placed under the kidney capsule of 10- to 12-wk-old female NZB/W mice (H-2d/z). Donor epithelium, equivalent to 1-2 lobes of neonatal thymus, was either irradiated (1300 rad.) or cultured for 7 days in order to minimise host-versus-graft reactions. Histological examination showed that the epithelium repopulated and remained in place until the end of the experiment, with no sign of rejection. Despite this, the treated animals lived no longer than the untreated or sham operated controls. Levels of anti-nuclear antibody and serum IgM (normally highly elevated in these animals) were not significantly different in any group.

Animals↗
PubMed1982

The nature of the autoantibody response to thyroglobulin in murine strains with high or low susceptibility to the experimental induction of autoimmune thyroiditis.

A sensitive three-layer solid phase immunoradiometric assay for estimating thyroglobulin antibodies in different mouse immunoglobulin subclasses was established and applied to study the subclass distribution of these antibodies in strains of mice differing in their susceptibility to the development of experimental autoimmune thyroiditis. Low response could not be ascribed to failure to produce a particular subclass. However, the absolute antibody levels in susceptible strains tended to be much higher, particularly in the IgG1, IgG2a and IgG2b classes 2 weeks after immunization. These differences in IgG1 and IgG2a persisted for a further 5 weeks but were less marked in the other subclasses. It would appear that antibody levels may be important in pathogenesis but since mice with high titres of thyroglobulin antibodies do not invariably develop thyroiditis, it is likely that further factors may be involved.

Animals↗
PubMed1981

Plasma exchange in systemic lupus erythematosus.

Eight out of 10 patients studied longitudinally received benefit from plasmapheresis. The patients were used as their own controls, being treated in a steady state as far as was possible. Levels of circulating complexes did not bear a close relationship with clinical results. On the evidence plasma exchange alone does not appear to represent an important part of the long-term management of patients with systemic lupus erythematosus but may well be of value in combination with other therapy.

Adult↗
PubMed1981

Synergy between IgG and monoclonal IgM antibodies in antibody-dependent cell cytotoxicity.

Hybridoma-derived mouse monoclonal IgM anti-ox erythrocyte (ORBC) antibodies, which differed in their ability to exhibit complement-mediated cytotoxicity, direct agglutination and sensitization of indicator cells for detection of receptors for IgM on erythrocytes, failed to mediate antibody-dependent cell cytotoxicity (ADCC) by human K cells. Polyclonal rabbit IgM anti-ORBC antibodies were also incapable of mediating ADCC. However, one of the IgM monoclonal antibodies studied (clone 100) was highly efficient in synergizing with IgG in ADCC, especially when the E rosette-forming enriched fraction was used as a source of effector cells. This synergy was greater after overnight incubation of the lymphocytes and was partially blocked by human IgM. Since all the monoclonal antibodies studied bound efficiently to target ORBC as determined by the additional binding of 125I-labeled anti-k antibodies, the synergy did not appear to be due to a quantitative difference in the binding capacity of the antibodies. That the synergistic effect of purified clone 100 IgM was not due to heterophile IgG antibody was indicated by its sensitivity to reduction and lack of binding to a protein A column. The data are discussed in terms of the possible in vivo relevance of IgG-IgM synergy to immune protection, especially during the development of a primary antibody response when limiting amounts of specific IgG antibodies could be made more effective with the more abundant IgM antibodies.

Animals↗
PubMed1981

An investigation of the clonality of human autoimmune thyroglobulin antibodies and their light chains.

Thyroglobulin antibodies in the sera from 31 patients with a variety of disorders were studied by isoelectric focusing. Only one gave a spectrotype indicative of a monoclonal response, the other 30 giving spectrotypes characteristic of polyclonal responses. There was evidence of clonal dominance in some of the sera and each gave a different spectrotype. Light chains were prepared from five thyroglobulin antibodies purified by affinity chromatography. There was no restriction in the spectrotypes when compared with light chains prepared from normal immunoglobulin.

Antibodies, Monoclonal↗