Biomedical subjects

C J Elson

Publications and source records attributed to C J Elson.

At least 127 records · Page 7Linked to original sources

PubMed1987

Murine T cells reactive against autologous erythrocytes: evidence for in vitro and in vivo priming with mouse and rat red blood cells.

Normal mice are shown to harbor T cells that can be sensitized to proliferate against autologous red blood cells (RBC). These autoreactive cells were primed in vitro and in vivo with mouse as well as heterologous rat RBC, the in vivo administration of which has been previously shown to trigger the production of auto-RBC antibodies. Two broad classes of specificity are detected following priming: T cells cross-reactive for similar determinants coexpressed by mouse and rat RBC, and T cells specific for antigens restricted to self-RBC. These findings indicate that clonal deletion of self-RBC-reactive T cells is far from complete. The comparison of different in vitro and in vivo immunization protocols revealed the possible existence of several levels of immunoregulatory control which may prevent the expression of autoimmunity by these T cells.

Animals↗

PubMed1987

Pharmacological modulation of erythrocyte autoimmune reactions in mice.

Injection of mice with rat erythrocytes induces both anti-rat and autoimmune anti-erythrocyte responses. The autoimmune response is under active suppression which can be demonstrated by transfer of spleen cells from immunised donors to naive recipients subsequently injected with erythrocytes. This system allows investigation of immunemodulatory agents on responses to self and non-self antigens in three ways the autoantibody and anti-rat erythrocyte responses in mice receiving the drugs and rat erythrocytes; the responses in mice receiving transferred cells from dosed immunised donors; and the responses in mice receiving transferred cells from non dosed immunised donors and themselves receiving erythrocytes plus drugs. The effect of a range of compounds with immunemodulatory activity was examined in the three test situations and both suppression and enhancement of the autoimmune response were observed. Comparison of effects on anti-rat and autoimmune antibody levels has confirmed previous results that these responses are subject to separate controlling mechanisms.

Animals↗

PubMed1987

Identification of rat erythrocyte antigens with a new non-radioactive immunoprecipitation technique.

In order to examine how rat erythrocytes stimulate erythrocyte autoantibody production at the molecular level, we have identified rat erythrocyte antigens by immunoprecipitation and western blotting using monoclonal antibodies and antisera. A novel non-radioactive immunoprecipitation technique was used, which employed biotin as a label and a luminescent detection system. The new method was validated by comparison with conventional immunoprecipitation using 125I. Glycophorins of relative molecular mass (Mr) 81,000 and 38,000 were found to be the major antigenic components of rat erythrocytes, while band 3 (the most abundant erythrocyte membrane protein) was not recognized by rat-specific antibodies. The same surface antigens were recognized by sera from mice producing erythrocyte autoantibodies and by sera from mice in which autoantibody production was suppressed. Nine other minor rat-specific antigens were identified by blotting, ranging in Mr from 23,000 to 147,000. Analysis of the integral membrane proteins of rat and mouse erythrocytes by sodium dodecyl sulphate (SDS) electrophoresis followed by silver or periodic acid-Schiff (PAS) stains revealed differences between the glycophorins, but not between rat and mouse band 3. Thus, the major antigenic differences correspond to discernible biochemical differences between rat and mouse erythrocyte sialoglycoproteins.

Animals↗

PubMed1987

Immunological involvement in the pathogenesis of pristane-induced arthritis.

Evidence is presented that the development of arthritis induced in mice by 2,6,10,14-tetramethylpentadecane (pristane) involves the immune response. Mice irradiated (500 rad) before injection of pristane failed to develop arthritis. By contrast, irradiated mice given lymphoid cells from normal donors and challenged with pristane developed arthritis. Other experiments showed that lymphoid cells from irradiated mice given pristane suppressed the development of arthritis in recipients challenged with pristane. Finally, the incidence of arthritis was significantly higher in CBA/Igb mice given pristane than in the allotypic congenic strain CBA/H, suggesting that a gene linked to the heavy chain immunoglobulin locus controls the development of arthritis.

Animals↗

PubMed1987

Isolation and analysis of complement activating aggregates from synovial fluid of patients with rheumatoid arthritis using monoclonal anti-C3d antibodies.

The complement activating aggregates in synovial fluids of patients with rheumatoid arthritis (RA) have been isolated using monoclonal IgM anti-C3d antibodies attached to solid phases, and the content of the material bound has been analysed. High levels of aggregated IgG bearing C3d were found in RA synovial fluids, and IgG was the major immunoglobulin bound from such synovial fluids by anti-C3d Sepharose. A strong correlation was shown between levels of aggregated IgG bearing C3d and complement activation, as judged by C3d levels. Significant (but less strong) relationships were also observed between C3d levels and both complement consuming and C1q binding activity. C3d levels and levels of aggregated IgG bearing C3d were both significantly associated with the numbers of polymorphonuclear leucocytes (PMNs) found in RA synovial fluids. From these results it is concluded that the aggregated immunoglobulins bearing C3d (particularly IgG) isolated from RA synovial fluids are responsible for activating complement and attracting PMNs into the joint space. Radioimmunoassay showed no correlation, however, between levels of aggregated IgG (or IgM) bearing C3d and rheumatoid factor (RF) activity bound by anti-C3d. In addition, the material bound by anti-C3d Sepharose from most synovial fluid polyethylene glycol precipitates did not contain either IgM or IgG RF. Thus both techniques show that the majority of complexes bearing C3d do not contain RF. As the complement fixing aggregates apparently contain only immunoglobulin and complement components the results raise the problem of how the aggregates are formed. It is suggested that RA IgG may remain aggregated after either antigen or antibody (RF) has dissociated from the complex.

Antibodies, Monoclonal↗

PubMed1986

Characterization of suppressor-inducer cells which control the production of rat erythrocyte-induced anti-erythrocyte autoantibodies.

Mice immunized with rat erythrocytes produce autoantibodies to their own red blood cells, distinct anti-rat agglutinins and autoantigen-specific suppressor cells. Suppressor cells were detected by adoptive transfer of rat erythrocyte-immunized spleen cells to naive recipients. Such recipients failed to make erythrocyte autoantibodies after immunization with rat erythrocytes although their anti-rat erythrocyte response was unimpaired. Depletion and enrichment studies were performed to identify the cell type(s) which transfer suppression. B cell depletion of rat erythrocyte-immunized spleen cells by passage over Ig/anti-Ig-coated bead columns abrogated the transfer of suppression. However, suppression was still transferred after rat erythrocyte immunized spleen cells were passed over beads coated with a complex of 4-azido-2-nitrophenyl (NAP)-mouse IgG-rabbit IgG anti-NAP suggesting that T cells bearing Fc gamma receptors are not responsible for suppression. Positively selected B cells from rat erythrocyte-immunized spleen cells caused some suppression of erythrocyte autoantibodies but only after high numbers of cells were transferred. Neither positively selected Lyt-1+2- nor Lyt-1-2+ T cell subpopulations transferred suppression. By contrast, rat erythrocyte-immunized spleen cells which contained a mixture of B memory and T cells were suppressive and retained their suppressor activity after removal of Lyt-1-2+ but not Lyt-1+2- cells. It is proposed that these Lyt-1+2-T cells belong to a distinct population of suppressor-inducer cells which together with memory B cells stimulate the generation of effector T suppressor cells in naive recipients.

Animals↗

PubMed1986

Proliferative responses of T-cell lines grown from joint fluids of patients with rheumatoid arthritis and other arthritides.

T-cell lines were established by culturing, in the presence of IL-2, mononuclear cells obtained from synovial fluids (SF) of most (77%) patients with rheumatoid arthritis (RA). By contrast, SF from patients with osteoarthritis and crystal synovitis rarely yielded lines. The cell lines were identified as T-cells because they express the CD3 surface antigen and either CD8 or CD4. The ability of the T-cell lines to react with putative antigens was tested using autologous Epstein-Barr virus transformed B-cells (EBV-B) as antigen presenting cells. IgG failed to stimulate proliferation of any RA patients' T-cell lines while Type II collagen stimulated T-cell lines from one RA patient and from one with osteoarthritis. Some T-cell lines (17/26) took up more tritiated thymidine after three days culture with a mixture of autologous SF and irradiated autologous EBV-B than with either alone. The effect could not be ascribed to a mitogen in the RA SF as the fluids failed to stimulate blood mononuclear cells. We consider that RA SF contain a T-cell growth factor which can only exert its effect through an antigen presenting cell (EBV-B).

Arthritis, Rheumatoid↗

PubMed1986

Fibronectin binding with immunoglobulin aggregates and its association with rheumatic disorders.

Fibronectin was shown to bind heat-aggregated, but not monomeric, human IgG, suggesting that fibronectin may bind directly to IgG immune complexes. The presence of material both binding and already containing fibronectin was demonstrated in polyethylene glycol precipitates of sera and synovial fluids from patients with rheumatoid arthritis (RA) and gout, but not normal sera. By contrast, complement-fixing complexes contained fibronectin in RA synovial fluids and sera, but not in sera and synovial fluids from other rheumatic disorders. It is considered that fibronectin binds to immune complexes in RA synovial fluids and sera but that some other, as yet unidentified material, is effective in binding fibronectin in sera and synovial fluids from patients with osteoarthritis and crystal synovitis.

Antigen-Antibody Complex↗

PubMed1986

Carrier-specific induction of suppressor cells controlling anti-erythrocyte autoantibody production in mice.

Mice immunized with rat erythrocytes develop anti-erythrocyte autoantibodies, distinct anti-rat erythrocyte agglutinins, and suppressor-inducer cells, which regulate the production of autoantibody but not anti-rat erythrocyte agglutinins upon transfer to naive recipients. In this report, we have tried to determine the specificity of the suppressor-inducer cells. CBA/N mice (which express an X-linked genetic B-lymphocyte defect) immunized with rat erythrocytes developed no autoantibodies but normal levels of anti-rat erythrocyte antibodies and suppressor-inducer cells, thereby suggesting that neither idiotypes on autoreactive B cells nor idiotypes on autoantibody itself, stimulate suppressor-inducer cells. In contrast, rat erythrocyte-primed spleen cells suppressed both a primary 2,4,6 trinitrophenyl (TNP) response and anti-erythrocyte autoantibody production (but not anti-rat erythrocyte antibodies) upon transfer to naive recipients and challenge with TNP-rat erythrocytes. It is considered that the suppressor-inducer cells are carrier-specific and that they are not stimulated by idiotypes on either autoantibody or autoreactive B cells.

Animals↗

PubMed1986

Relationship between non-antigen-specific immunodepression and persisting immune complexes induced by pertussis in mice.

A temporal relationship has been demonstrated between persisting immune complexes and non-antigen-specific immunodepression. Mice were given intraperitoneal injections of Bordetella pertussis at weekly intervals. After 7 weeks they developed circulating immune complexes, the levels of which increased with continued administration of pertussis. The increase in immune complex levels was accompanied by a diminished primary immune response to intraperitoneally injected sheep erythrocytes (SRBC) as judged by a reduction in their direct and indirect plaque-forming cell response and serum agglutination titres. Spleen cells from immunodepressed pertussis-treated mice were transferred to irradiated normal recipients and displayed a normal response to SRBC. By contrast, spleen cells transferred from normal donors to irradiated pertussis-treated recipients had an impaired response to SRBC. Thus, the immunodepression caused by pertussis treatment is a property of the environment and not the lymphocytes themselves. It is considered that chronic circulating immune complexes induced by pertussis administration may cause non-antigen-specific immunodepression.

Animals↗

PubMed1985

Functional differences between B cell-depletion techniques in removing memory B cells. Relevance to anti-erythrocyte autoantibody-specific suppressor cells.

The efficiency of a number of B cell-depletion techniques was examined in a functional assay. CBA (Iga) mice were primed with rat erythrocytes and their spleen cells transferred, before and after B cell depletion, to mice of the allotype-congenic strain Igb. The recipients were challenged with rat erythrocytes and their anti-erythrocyte autoantibody response was measured together with the donor (Iga) and host (Igb) anti-rat erythrocyte antibody levels. Transferred unseparated cells suppressed erythrocyte autoantibodies and produced high levels of anti-rat erythrocyte antibodies. Transfer of panned, rosetted or nylon wool-passaged cells neither altered donor anti-rat erythrocyte antibody levels nor abrogated suppression. By contrast, passage of rat erythrocyte-primed B cells over Ig-anti-Ig-coated beads resulted in removal of donor rat-primed B cell activity and loss of suppressor cells. The B cell-depletion techniques were effective at removing B cells as judged by the reduced number of fluoresceinated anti-Ig-labeled cells among unbound cells although analysis on a fluorescein-activated cell sorter revealed that the most effective method was depletion on Ig-anti-Ig-coated beads. B cell depletion by panning removed the capacity of virgin but not primed cells to make adoptive antibody responses after transfer suggesting that the primed cells most efficient in adoptive transfer have a lower density of surface Ig than virgin cells. Treatment of donors with drugs which abrogated transferrable suppression of erythrocyte autoantibodies did not alter donor anti-rat erythrocyte antibody levels in recipients. It is considered that rat primed B cells are involved in the suppression of erythrocyte autoantibodies by acting as selective antigen-presenting cells for T suppressor inducer cells, rather than through an anti-rat erythrocyte antibody feedback mechanism.

Animals↗

PubMed1985

A new assay for IgG rheumatoid factor activity and its use to analyse rheumatoid factor reactivity with human IgG isotypes.

A new assay for IgGRF activity is described which employs human IgGFc as the antigen and a radiolabelled monoclonal antibody directed against human IgG (CHI domain) as the developing antibody. Using this assay IgGRF activity against human IgG isotypes was measured and most sera from RA patients were shown to react predominantly with IgG1 and IgG2 but few reacted with IgG3 and IgG4. The same sera were tested for IgMRF to the IgG isotypes. IgG2 was the best antigen, IgG1 and IgG4 were less so and reactivity with IgG3 was the lowest. IgGRF without associated IgMRF was obtained, its specificity compared to that of IgMRF, and found to be broadly similar. With the new assay high levels of serum IgGRF were found in those RA patients with extraarticular disease but not in RA patients with synovitis alone.

Antibodies, Monoclonal↗

PubMed1985

Complement activating properties of complexes containing rheumatoid factor in synovial fluids and sera from patients with rheumatoid arthritis.

The relationship between complexes containing rheumatoid factor and complexes activating complement was examined in synovial fluids and sera from patients with rheumatoid arthritis (RA). In each case this was performed by quantifying the amount of rheumatoid factor bound by solid phase Fab'2 anti-C3 and/or solid phase conglutinin. Both anti-C3 coated and conglutinin coated microtitre plates bound high levels of complexes containing rheumatoid factor from sera of RA patients with vasculitis. Unexpectedly, these complexes were detected in synovial fluids from only a minority of RA patients with synovitis. However, RA synovial fluids did contain other complexes as shown by the presence of complement consuming activity, C1q binding material and immunoglobulin attaching to conglutinin. It is considered that in RA synovial fluids the complexes containing RF and those activating complement are not necessarily the same whilst in vasculitic sera the complexes containing rheumatoid factor also activate complement.

Adult↗

PubMed1984

Mononuclear phagocytes in rheumatoid arthritis: Fc-receptor expression by peripheral blood monocytes.

Fc receptor expression by enriched monocytes from rheumatoid arthritis (RA) patients and age and sex matched controls (healthy subjects) was compared by measuring the uptake of IgG on monocytes in a competitive radioassay. The association constant (Ka) between IgG and the monocytes and the number of Fc binding sites per cell was calculated from Scatchard plots of 4 degrees C binding data. RA monocytes had increased expression of Fc receptors as compared with those of controls. This increase was particularly pronounced in those RA patients affected by extra-articular disease. There were significant correlations between the numbers of Fc receptors on monocytes and both C1q binding and anticomplementary activity but none between monocyte Fc receptor numbers and serum rheumatoid factors (IgG and IgM). It is considered that monocyte handling of circulating immune complexes is unimpaired in RA and that monocytes make an adaptive response to increased levels of immune complexes.

Aged↗

PubMed1984

Clearance and organ localization of particles and soluble complexes in mice with circulating complexes.

The clearance and organ localization of a number of substances cleared by either Fc-dependent or -independent mechanisms was studied in normal mice and in mice with endogenously produced persistent circulating complexes. Clearance of covalent dimers of mouse IgG, chicken IgG and ovalbumin were no different between the two groups of mice. By contrast, hepatic and splenic uptake of dimeric mouse IgG (but not of chicken IgG or ovalbumin dimer) was impaired in the mice with persisting complexes. Surprisingly the rate of clearance of sheep red blood cells (SRBC) was increased in mice with persisting complexes as was hepatic uptake of polyvinyl pyrrolidone. It is suggested that the mononuclear phagocytes of mice with persistent circulating complexes are non-specifically stimulated while their ability to take up soluble complexes by Fc-dependent attachment is selectively impaired.

Animals↗

PubMed1983

Preparation of covalent IgG complexes of defined size and their clearance from the circulation of mice.

Covalent complexes of various sizes were made by coupling the photosensitive hapten, NAP (4-azido-2-nitrophenyl), to rabbit IgG and reacting the conjugates with rabbit anti-NAP antibodies. The resultant oligomers were stable, being eluted as the same discrete peaks after chromatography on gels both before and after injection into mice. Tests of their biological properties showed they fixed guinea pig complement in vitro in a size-dependent manner. Normal mice and mice with chronic endogenous circulating complexes cleared the oligomers according to size in a manner best described by a two-component exponential curve. There was no difference in the clearance rates between the two groups of mice. The advantages of these model complexes for examining the effect of circulating complexes on the mononuclear phagocyte system are discussed.

Animals↗

PubMed1983

Complement-activating rheumatoid-factor-containing complexes in patients with rheumatoid vasculitis.

The role of complement and rheumatoid factor in immune complexes was examined in patients with a variety of rheumatic diseases. This was done by assessing the amount of rheumatoid factor (RF) bound from sera by F(ab)2 anti-C3 attached to a solid matrix. High levels of RF bound to C3 were detected in patients with rheumatoid arthritis complicated by vasculitis but rarely and in lower levels in patients with synovitis, ankylosing spondylitis, and systemic lupus erythematosus. The activity was bound to anti-C3 through anti-C3 antibodies because little was bound by normal F(ab)2 and was evidently complexed in the sera before in-vitro testing, since it was precipitated by 2 . 5% polyethylene glycol and sedimented with high molecular weight material on sucrose density gradient ultracentrifugation. It is considered that RF-containing complexes are present in vasculitic sera and have the potential to bind complement in vivo.

Antigen-Antibody Complex↗

PubMed1982

Continuous production of anti-host IgG antibodies contained in circulating IgG-anti-IgG complexes.

Weekly injection with antibody-coated pertussis led to the chronic production of serum complexes in mice. Mice bearing one allotype. Iga, received spleen cells from a congenic strain bearing another allotype, Igb, and weekly injections with Iga-coated pertussis. The serum complexes from these mice and from those receiving challenges alone were separated by ultracentrifugation at neutral and acid pH on sucrose density gradients and their fractions tested for their anti-Iga and Iga content. This revealed the presence of anti-host (Iga) allotype antibodies in fractions from mice that had received Igb cells but not from mice given Iga-coated pertussis alone. Iga allotype was detected in fractions from both groups. It is considered that anti-host allotype antibodies are continuously produced but that they cannot be detected in unfractionated serum because the antibody forms complexes with Iga. These findings are discussed in relation to rheumatoid disease in humans.

Animals↗