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Biomedical subjects

E Mozes

Publications and source records attributed to E Mozes.

At least 127 records · Page 7Linked to original sources
PubMed1989

The effects of methotrexate on the production and activity of interleukin-1.

To explore the possibility that the mechanism of action of methotrexate (MTX) in rheumatoid arthritis (RA) is related to modulation of interleukin-1 (IL-1), the effects of MTX on IL-1 production and activity were evaluated. Human peripheral blood mononuclear cells and murine peritoneal and splenic cells were stimulated by lipopolysaccharide to produce IL-1. No inhibition of IL-1 synthesis or secretion caused by MTX treatment could be demonstrated either in vitro or in vivo, in patients with RA or in mice treated with MTX. We did show, however, that MTX had an inhibitory effect on IL-1 activity in 2 assays that demonstrate 2 different functions of IL-1. In a 2-step assay using LBRM-33-1A5 (1A5) and CTLD cells, MTX inhibited the secretion of IL-2 by 1A5 lymphoma cells in response to phytohemagglutinin and IL-1. In an assay using D10.G4.1 (D10) cells, MTX inhibited IL-1-induced proliferation of the D10 T cell clone. No effect of the drug on IL-2 activity was observed. The results demonstrate that MTX is capable of inhibiting some IL-1 activities without affecting IL-1 production or secretion. We propose that the inhibition of IL-1 activity or IL-1-dependent events may be one of the mechanisms of action of MTX in RA.

Animals↗
PubMed1989

The role of anti-idiotypic antibodies in the induction of experimental systemic lupus erythematosus in mice.

We have recently reported the induction of experimental systemic lupus erythematosus (SLE) in mice by a human anti-DNA monoclonal antibody (mAb) that bears a common idiotype, the 16/6 Id. In the present report we investigated the role of the idiotypic network in the induction of experimental SLE by using a murine anti-idiotypic mAb specific for the 16/6 Id. This anti-idiotypic mAb induced experimental SLE similarly to the 16/6 Id. Thus, following immunization, in addition to 16/6 Id+ antibodies, the mice produced antibodies to various nuclear antigens: single-stranded DNA, double-stranded DNA, poly(I), poly(G), Ro, La, Sm and ribonucleoproteins. Similarly to the 16/6 Id-immunized mice, the mice injected with the anti-16/6 Id mAb exhibited elevated erythrocyte sedimentation rate and leukopenia. The murine anti-16/6 Id mAb was found to be more effective than the 16/6 Id, in causing earlier onset of proteinuria and renal damage. These results suggest that the idiotypic network and particularly anti-idiotypic antibodies specific for anti-DNA common idiotypes found in SLE, play an important role in the induction of SLE in mice.

Animals↗
PubMed1989

The role of the idiotypic network in the induction of experimental systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) has been induced in C3H.SW mice by their immunization with a human monoclonal anti-DNA antibody that bears a common idiotype-16/6 Id. Following immunization, high levels of murine anti-16/6 and anti-anti-16/6 antibodies were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with ssDNA, dsDNA, poly(I), poly(G), RNP, Ro, and La were also observed. The serological findings were associated with significant proteinuria, leukopenia, and elevated erythrocyte sedimentation rate. Immune complex deposition in the glomerular mesangium and sclerosis of the glomeruli were demonstrated. To study whether or not anti-idiotype antibodies are involved in the induction of the disease, a murine monoclonal antibody against the 16/6 Id was prepared and injected into C3H.SW mice. The anti-16/6 Id antibody induced experimental SLE similarly to the 16/6 Id with an accelerated kidney pathology. A study performed on different mouse strains indicated that the susceptibility to the induction of SLE by the 16/6 Id is strain dependent and directly correlates to their ability to produce anti-16/6 Id specific antibodies.

Animals↗
PubMed1988

In vitro T-cell functions specific to an anti-DNA idiotype and serological markers in patients with systemic lupus erythematosus (SLE).

The human monoclonal autoantibody 16/6 is a common anti-DNA idiotype found to have clinical relevance in patients with systemic lupus erythematosus (SLE). Therefore the ability of peripheral blood T cells of SLE patients and healthy controls to proliferate and to produce helper T-cell factors following stimulation with this idiotype was tested. It was found that T cells of 75% of healthy donors proliferated to the 16/6 idiotype, whereas only 22% of SLE patients responded to this idiotype by proliferation. On the other hand, the capability to produce T-cell helper factors specific to the 16/6 idiotype was found in a higher percentage of SLE patients (48%) as compared to healthy controls (31%). The low frequency of proliferative responses in SLE patients might be due either to the chronic exposure to the 16/6 idiotype or to the production of antiidiotype antibodies against the 16/6 idiotype, which interfere with the response to the latter stimulator.

Adolescent↗
PubMed1988

Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype.

Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. We herewith report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens [Sm, SS-A (Ro), and SS-B (La)], and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE.

Animals↗
PubMed1988

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

To investigate which parts of the acetylcholine receptor are involved in the initiation and development of myasthenia gravis (MG), peptides representing different sequences of the human acetylcholine receptor alpha-subunit were synthesized. These peptides were tested for their ability to stimulate T cells of myasthenic patients and healthy control patients in proliferation assays and to bind to sera antibodies. Three of eight peptides discriminated significantly between the two groups in the proliferation assay, as well as in their ability to bind to serum antibodies. HLA-DR3 and DR5 were associated with proliferative responses to specific AChR peptides in the group of myasthenics. Acetylcholine receptor epitopes that might play a specific role in myasthenia gravis thus were demonstrated.

Amino Acid Sequence↗
PubMed1987

Characterization and biologic activities of an anti-idiotype-specific T cell line and its derived clones.

Monoclonal anti-idiotypic antibodies were prepared against monoclonal antibodies (mAb103) specific to the synthetic polypeptide antigen (T,G)-A-L. A cell line was established by the stimulation of C3H.SW mouse T cells with one of the monoclonal anti-idiotypes (mAbA-6) that reacted with both mAb103 and conventional (T,G)-A-L-specific antibodies. The T cell line proliferated specifically in the presence of the homologous mAbA-6 and to a lesser degree when triggered with (T,G)-A-L. The line could help (T,G)-A-L primed B cells in the production of (T,G)-A-L-specific antibodies when stimulated in vitro with either (T,G)-A-L or mAbA-6. Clones obtained from the line were stimulated and maintained in culture in presence of mAbA-6 whereas others were stimulated and grown in the presence of (T,G)-A-L. Both types of clones proliferated only in the presence of mAbA-6 although (T,G)-A-L could inhibit efficiently and specifically the latter proliferation. A significant number of the (T,G)-A-L-stimulated clones could collaborate with (T,G)-A-L primed B cells in the presence of either (T,G)-A-L or mAbA-6 for the production of specific antibodies. Immunoblotting experiments indicated that mAbA-6 reacted with both the T cell receptor of the mAbA-6-specific T cell line and of a (T,G)-A-L-specific T cell line but not with that of a line specific to a nonrelated antigen.

Animals↗
PubMed1987

Analysis of the antigen specific helper T cell function and HLA-DR of Israeli patients with rheumatoid arthritis (RA).

Forty-three patients with rheumatoid arthritis (RA) were studied for their ability to respond to the synthetic polypeptide antigen (T, G)-A-L as measured by the production of a T cell helper factor by their antigen activated T cells. Sixteen patients (37%) responded to (T, G)-A-L by the production of an antigen specific helper T cell factor, a percentage not significantly different from healthy donors. The production of antigen specific T cell helper factors was affected, although not significantly, by immune modulating drugs and by the presence of rheumatoid factor in sera of patients. The high incidence of HLA-DR 4 reported for RA patients was not observed in this group of RA patients.

Adult↗
PubMed1986

Functional requirements of (Phe, G)-A--L-specific T-cell clones of (H-2b X H-2k)F1 origin.

T-cell clones specific for the synthetic polypeptide antigen poly(LPhe, LGlu)-poly(DLAla)--poly(LLys) of (C57BL/6 X C3H/HeJ)F1 origin were tested for their biological activities. One group of clones was restricted in its proliferative response to the H-2b haplotype, the second to the H-2k haplotype, and the third to the F1 unique Ia determinants. All the clones which proliferated in response to antigen secreted interleukin-2 (IL-2) following stimulation. The H-2 restriction of the IL-2 secretion was the same as that of the proliferation. Two of the clones tested, C.6 and C.10, could provide help to B cells in antibody production. However, the genetic restriction profile of the helper activity was less stringent than that for the proliferative response. Thus, C.6, which proliferated in the presence of F1 antigen-presenting cells only, could help B cells and accessory cells of C3H/HeJ. C.10, which was restricted in its proliferative response to the H-2b haplotype, could collaborate with B cells and accessory cells of the H-2k haplotype as well. The antibody response of both clones was restricted to the parental or F1 strains.

Animals↗
PubMed1986

Genetic control of HLA-linked immune responsiveness to (H,G)-A-L.

Fifty-three donors belonging to seven families were tested for their immune response potential to (H,G)-A-L. Most of these donors had been previously tested for their ability to respond to (T,G)-A-L and were all HLA typed as well. The heredity of the ability to respond to (H,G)-A-L by the production of an antigen-specific helper T cell factor is compatible with an autosomal dominant trait linked to HLA. The genotype of an HLA-A/B recombinant individual suggested that a gene controlling the immune response to (H,G)-A-L is linked to HLA-A. Lod scores also suggested a linkage between immune response potential to (H,G)-A-L and HLA-A. The different patterns of responses to (T,G)-A-L and (H,G)-A-L observed in many individuals are compatible with the notion that separate loci are governing the immune responses to the two synthetic polypeptides.

Female↗
PubMed1986

Analysis of the biological functions and fine specificity of (T,G)-A--L specific T cell clones.

Two T cell lines, TPB1 and TPB2, specific for the synthetic polypeptide antigen (T,G)-A--L, were established from (T,G)-A--L primed lymph node cells of C3H.SW(H-2b) mice. Both lines proliferated in the presence of (T,G)-A--L, helped in antibody production in vitro, and secreted IL2 upon stimulation with antigen. The lines differed in the fine specificity of their responses to antigenic stimulation. The line with the broader specificity TPB2 was cloned by limiting dilution, and its derived clones were analyzed. No efficient manifestation of both proliferative activity and helper function could be detected in a single clone. Most of the clones were highly specific to (T,G)-A--L, although 2 of them cross-reacted with the closely related polypeptide (Phe,G)-A--L. Individual clones could trigger B cells for the production of antibodies of the IgM and IgG classes. All helper clones secreted (T,G)-A--L specific helper factors. No correlation was found between efficient secretion of IL2 by the clones and their other biological functions.

Animals↗
PubMed1986

Antigen-presenting cells in human decidual tissue.

The responses of peripheral blood human T lymphocytes supported by decidual antigen-presenting cells (DAPCs) to a variety of immunogenic stimuli were studied and compared to those of T cells supported by peripheral blood antigen-presenting cells (PAPCs). Antigen-presenting cells were isolated from early normal decidual tissue or peripheral blood by elution with ethylenediamine tetraacetic acid of cells that after Ficoll-Paque separation bear receptors for all have bound to fibronectin. DAPCs pulsed with soluble or particulate antigens induced proliferation of T cells with an efficiency equivalent to PAPCs. Decidual tissue APCs also showed the ability to stimulate auto- and alloreactivity. Treatment with anti-human lymphocyte antigen (HLA) class II antibody and ultraviolet radiation resulted in substantial inhibition of the accessory cell function of DAPCs as well as of PAPCs. Bromodeoxyuridine and light treatment of alloreactive T cells generated in vitro was used to demonstrate that DAPCs primed with a synthetic polypeptide antigen (T,G)-A-L can stimulate only HLA class II-compatible T lymphocytes.

Adult↗