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Biomedical subjects

E Mozes

Publications and source records attributed to E Mozes.

At least 109 records · Page 6Linked to original sources
PubMed1991

Specific proliferative responses following the induction of experimental SLE in mice.

We have previously reported the induction of experimental systematic lupus erythematosus (SLE) in mice by immunization with a human monoclonal antibody that expresses a common anti-DNA idiotype (16/6 Id). Following immunization, antibodies directed against various nuclear autoantigens could be detected in the sera of the mice. In the present study, we investigated the proliferative responses of lymph node cells to one particular autoantigen (DNA) following the induction of experimental SLE. Cells reactive with ssDNA could be detected following immunization of BALB/c mice with the 16/6 Id. The appearance of these DNA-reactive cells succeeded the appearance of 16/6 Id-specific cells. The activation of this subset of autoreactive cells could be achieved only by the immunization of the mice with the 16/6 Id, but not by their immunization with DNA, thus suggesting that the induction of experimental SLE is associated with the alteration of the low responsive potential of the mice to DNA.

Amino Acid Sequence↗
PubMed1991

Progressive immune dysfunction in cats experimentally infected with feline immunodeficiency virus.

Within 6 months of infection with the Petaluma isolate of feline immunodeficiency virus, specific-pathogen-free domestic cats exhibited a decrease in the percentage and number of circulating CD4+ lymphocytes and in the CD4+/CD8+ T-cell ratio, along with a marginally significant depression of pokeweed mitogen-induced lymphocyte proliferation in vitro. There was no loss of responsiveness to concanavalin A during this stage, and the cats were capable of mounting a satisfactory antibody response to a T-dependent, synthetic polypeptide immunogen. The pokeweed mitogen response deficit became clearly demonstrable by 11 to 12 months postinfection. A decline in the lymphocyte proliferative response to concanavalin A and a diminished ability to mount an in vivo antibody response to the T-dependent immunogen evolved by 25 to 44 months postinfection. Virus infection did not affect the ability of cats to mount an antibody response to a T-independent synthetic polypeptide immunogen. These data indicate that feline immunodeficiency virus produces a slowly progressive deterioration of T-cell function but does not affect the ability of B cells to recognize and respond to a T-independent antigenic stimulus.

Amino Acid Sequence↗
PubMed1991

Regulatory T cell activity specific to human type II and III collagens in rheumatoid arthritis.

Fifty-one patients with rheumatoid arthritis (RA) were examined for their immune response potential to human collagen type II and III. It was found that T cells of 57% of patients with RA proliferated to collagen type III whereas only 27% of T cells of patients with osteoarthritis (OA) and healthy controls responded to this antigen by proliferation (p less than 0.04). A lower percentage (38%) of patients with RA had proliferative responses to collagen type II in comparison to 17% of responders in healthy controls. The capability to produce T cell helper factors specific to collagen type III was found to be significantly higher in patients treated with nonsteroidal antiinflammatory drugs (NSAID) (60%) in comparison to patients with OA (16%) and healthy controls (13%). Immunoregulatory drugs affected the specific T helper function in response to collagen type III but did not change the proliferative responses to collagen type II and III in patients with RA. HLA analyses revealed a significant difference in the frequency of HLA-DRw10 between our sample of patients with RA and healthy controls.

Antibody Formation↗
PubMed1991

Idiotype specific T-cell lines inducing experimental systemic lupus erythematosus in mice.

Immunization of mice with either antibodies bearing the 16/6 idiotype (16/6 Id) or anti-idiotypic antibodies against the 16/6 Id induces experimental systemic lupus erythematosus (SLE). We report here the establishment and characterization of 16/6 Id-specific T-cell lines from C3H.SW (H-2b) and BALB/c (H-2d) mice. Both lines proliferate specifically in response to the 16/6 Id in an H-2-restricted manner. The injection of 16/6 Id-specific T cells into syngeneic mice led to the development of experimental SLE. Furthermore, inoculation of the 16/6 Id-specific T-cell line derived from C3H.SW mice into the H-2 compatible C57BL/6 mice, which are non-responders to the 16/6 Id, induced experimental SLE. This report provides direct evidence for the role of idiotype-specific T cells in the induction of experimental SLE.

Animals↗
PubMed1990

Monoclonal anti-La antibody derived from a mouse with experimental SLE is similar to human anti-La antibodies.

The La antigen is a highly conserved protein, originally defined by sera of patients with Sjögren's syndrome or systemic lupus erythematosus (SLE). In the present study, we have produced and characterized a monoclonal anti-la antibody derived from mice with experimental SLE. The induction of SLE in these mice was achieved by their immunization with a murine monoclonal anti-idiotypic antibody against a common idiotype (16/6 Id) found in SLE patients. The monoclonal anti-La antibody derived from these mice was found to be virtually identical to the anti-La antibodies found in human autoimmune sera. First, its binding to different nuclear extracts, as well as to protease-digested HeLa nuclear protein extracts, was found to be identical to that of human anti-La antibodies. Second, an inhibition study on blotted proteins demonstrated a very close relationship between the epitopes recognized by the murine monoclonal anti-La antibody and the human anti-La serum. Third, the monoclonal anti-La antibody was found by immunofluorescence to be directed against a nuclear antigen that gave a speckled pattern. Finally, the monoclonal anti-La antibody immunoprecipitated the La-associated small RNAs. This report provides evidence for the similarity of murine anti-La antibody produced in experimental SLE and human anti-La antibodies formed in autoimmunity.

Animals↗
PubMed1990

Induction of experimental systemic lupus erythematosus in mice by immunization with a monoclonal anti-La autoantibody.

Experimental systemic lupus erythematosus (SLE) in mice can be induced by immunization either with a human monoclonal anti-DNA antibody bearing the 16/6 idiotype (16/6 Id) or with a mouse monoclonal anti-idiotypic antibody specific for the 16/6 Id. In the present report we investigated the pathogenic role of a monoclonal anti-La autoantibody in the induction and mediation of experimental SLE in mice. The monoclonal anti-La antibody was derived from a mouse in which experimental SLE was induced by immunization with the monoclonal anti-16/6 Id antibody. Following immunization with the anti-La antibody the mice produced antibodies to double-stranded DNA, single-stranded DNA, Sm, SS-A/Ro, SS-B/La, and ribonucleoprotein. Furthermore, even though the anti-La antibody does not express nor react with the 16/6 Id, the immunized mice produced high titers of anti-16/6 Id antibodies as well as 16/6 Id bearing antibodies. Four months following immunization the mice exhibited significant proteinuria, and kidney sections revealed immune complex deposits on the basement membrane of the glomeruli. These results suggest that anti-La autoantibodies are involved in the induction and mediation of SLE in mice.

Animals↗
PubMed1990

Inhibition of T cell proliferation specific for acetylcholine receptor epitopes related to myasthenia gravis with antibody to T cell receptor or with competitive synthetic polymers.

Long-term T cell lines and clones of C3H.SW origin specific to synthetic peptides representing immunogenic epitopes of the human aetylcholine receptor alpha-subunit were established. Using these lines and clones, it was possible to characterize the T cell recognition process of myasthenic epitopes. Testing a panel of N-and/or C-terminal truncated peptides it could be demonstrated that the deletion of the two C-terminal amino acids of peptides p195-212 and p259-271 resulted in a loss or reduction of the stimulatory capacity of the peptides towards the specific T cell lines. In contrast, no substantial effect on the stimulation of the line could be observed by shortening peptide p195-212 by up to five amino acids at the N-terminal end. The proliferation of T cell lines and clones specific to peptide p195-212 was inhibited by a mAb directed against the V beta 8 region of the T cell receptor. Furthermore, it was possible to block the peptide-specific proliferative responses of the lines and clones by the I-Ab restricted synthetic polypeptide (T, G)-A--L but not by the I-Ak restricted polypeptide antigen (H,G)-A--L. Similarly, p195-212 inhibited the proliferative response of the TCSW259-271 T cell line and p259-271 inhibited the specific proliferative response of the TCSW195-212 line. Moreover, the C-terminal shortened peptides inhibited significantly the in vitro stimulation of the T cell lines by the immunogenic peptides p195-212 and p259-271. The inhibition by the synthetic peptides or by (T,G)-A--L may be due to competitive blockade of the MHC binding site for the T cell line stimulating AChR peptides.

Amino Acid Sequence↗
PubMed1990

Pathogenic idiotypes of autoantibodies in autoimmunity: lessons from new experimental models of SLE.

Systemic lupus erythematosus (SLE) is considered a classical autoimmune disease that involves many biological systems. Similar to other autoimmune conditions, its etiology is multifactorial entailing genetic, environmental, hormonal, and immunologic factors. In this review we demonstrate that by using a pathogenic idiotype of anti-DNA autoantibodies, it is possible to explain some of the pathogenesis and diversity of clinical and serological manifestations reported by SLE patients. The 16/6 idiotype (Id) is a representative pathogenic idiotype of anti-DNA autoantibodies. The serum titers of 16/6 Id in SLE patients correlate with clinical activity of the disease, and are deposited in afflicted tissues in SLE patients. SLE was experimentally induced in naive mice after immunization with 1 microgram of the Id. The disease is characterized clinically (proteinuria), serologically (e.g., anti-dsDNA, anti-Sm antibodies), and by pathological findings (e.g., deposition of 16/6 Id in the kidneys). The condition can be induced by other human and mouse antibodies carrying the 16/6 Id, as well as by mouse antimonoclonal-16/6 Id and by T cell lines and clones specifically reactive with 16/6 Id. There are strain-dependent differences in susceptibility to the induction of systemic lupus erythematosus (SLE). Induction of SLE is directly correlated with the ability to respond to the 16/6 idiotype (or 16/6 Id)2 by anti-Id antibody production. It is easier to induce the disease in females, and it can be modulated by manipulation of sex hormones. Being able to identify the pathogenic idiotype allowed us to generate T suppressor (Ts) cells specific for the 16/6 Id. Treatment of mice with these T cells abrogated the disease. Our studies point to the importance of pathogenic idiotypes of autoantibodies in autoimmunity, which suggests that SLE may represent a dysregulation of a functional network of idiotypes-anti-idiotypes interactions among autoreactive B cells, T helper cells, and T suppressor cells.

Animals↗
PubMed1990

Anti-DNA idiotype- and anti-idiotype-specific T cell responses in patients with systemic lupus erythematosus and their first-degree relatives.

We examined the proliferative responses of T cells of patients with systemic lupus erythematosus (SLE), their first-degree relatives, and healthy donors, to a human monoclonal antibody that bears a common anti-DNA idiotype, 16/6 Id, and to a murine, 16/6 Id-specific, monoclonal antibody. Both 16/6 Id+ and 16/6 Id-specific antibodies were previously shown to be involved in the induction of experimental SLE in mice. Here we show that T cells of fewer SLE patients, as compared with healthy donors, could proliferate to both antibodies. The difference between T cell responses of patients and controls to the 16/6 was found to be significant. The proliferative responses of T cells of first degree relatives of SLE patients to the anti-16/6 Id were found to be significantly lower compared with the responses detected in healthy donors and in SLE patients. The responses of T cells of SLE relatives to the 16/6 Id were found to be lower than those of healthy donors, but this difference was not significant. The present study suggests a possible involvement of T cells, and specifically of idiotype and anti-idiotype specific T cells, in SLE.

Antibodies, Anti-Idiotypic↗
PubMed1990

The effect of the immunomodulator agent AS101 on interleukin-2 production in systemic lupus erythematosus (SLE) induced in mice by a pathogenic anti-DNA antibody.

The role of the synthetic immunomodulator AS101 on the production of interleukin-2 (IL-2) by spleen cells of mice with SLE was investigated. BALB/c female mice, in which SLE was induced by immunization with the pathogenic idiotype of anti-DNA antibody 16/6 Id were treated with AS101 for 7 weeks 2 and 4 months after induction of the disease. The ability of the splenocytes of the mice with SLE to produce IL-2 was restored after administration of AS101. This effect was particularly impressive when the 7-week AS101 treatment was initiated 4 months after immunization. Despite its beneficial effect on IL-2 production, AS101 exerted no influence on the titres of autoantibodies in the sera of the mice. It also had no effect on clinical parameters of SLE, such as the increased sedimentation rate, proteinuria and low white blood cell counts. Our data indicate that defective IL-2 production in SLE is probably secondary to other disease processes and is not necessarily associated with the production of autoantibodies in this disorder.

Adjuvants, Immunologic↗
PubMed1990

The importance of the pathogenic 16/6 idiotype in the induction of SLE in naive mice.

We have previously demonstrated the pathogenicity of the common anti-DNA idiotype designated 16/6 Id. Immunization of naive mice with the 16/6 Id induced SLE-like disease characterized by serological (e.g. anti-dsDNA and anti-Sm auto-antibodies), clinical (increased ESR, leucopenia and proteinuria), and pathological (16/6 Id deposition in kidneys) parameters. To elucidate further the role of the 16/6 Id in SLE induction the following studies were carried out: BALB/c mice were immunized with SA-1, a human anti-DNA monoclonal antibody carrying the 16/6 Id; TB-68, a mouse monoclonal anti-tuberculosis (TB) glycolipid, which binds dsDNA and carries the 16/6 Id; TB-72, a mouse monoclonal anti-TB glycolipid that binds DNA and does not harbour the 16/6 Id; and 4B4, a human anti-Sm antibody that carries the 16/6 Id. SLE was induced in BALB/c mice only when immunized with SA-1, TB-68, and 4B4, namely antibodies with diverse binding capacities albeit having the 16/6 Id. Our studies further support previous evidence on the pathogenic role attributed to the 16/6 Id in SLE, and suggest that SLE is most probably an idiotype-induced disease.

Animals↗
PubMed1990

The autoimmune response of different mouse strains to T-cell epitopes of the human acetylcholine receptor alpha subunit.

The specific recognition of the acetylcholine receptor and its alpha-subunit by T cells derived from patients with myasthenia gravis or mice with experimental autoimmune myasthenia gravis raises the question of the role of autoreactive T cells in the myasthenic process. Sequences of the acetylcholine receptor alpha-subunit previously shown to be immunogenic in myasthenic patients were tested for their immunogenicity in various inbred mouse strains. High, intermediate and low T-cell proliferative responses could be observed to peptides representing sequences 195-212 and 259-271 of the human acetylcholine receptor alpha-subunit. Following immunization with the Torpedo acetylcholine receptor, lymphocytes of SJL mice proliferated efficiently to p 195-212 but not to p259-271. On the other hand, lymph node cells of BALB/c mice responded well to p259-271 but not to p195-212. Thus, the influence of the genetic make-up of the examined mice on the immune response to the two peptides could be clearly demonstrated by the existence of strain-dependent immunodominant and cryptic regions on the autoantigen. The differences between the strains were less pronounced when antibody responses were measured to these two T-cell epitopes, although a partial correlation with the proliferative responses could be observed. It can be concluded that epitopes specifically recognized by T lymphocytes of patients with myasthenia gravis also represent specific T-cell epitopes in the autoreactivity to the acetylcholine receptor in mice and that immune responsiveness to these peptides is influenced by the genetic make-up of the responding mouse strains.

Animals↗
PubMed1990

The genetic regulation of the induction of experimental SLE.

We have recently reported the induction of systemic lupus erythematosus (SLE) in C3H.SW female mice by their immunization with a human monoclonal anti-DNA antibody that bears a common idiotype termed 16/6 Id. In the present study, the ability to induce experimental SLE in seven inbred mouse strains by immunization with the 16/6 Id was examined. Two out of the seven strains failed to develop the disease. These two strains did not produce antibodies specific to the 16/6 Id, while the other five strains produced high titres of anti-16/6 Id antibodies. The anti-16/6 Id antibody response, followed by the induction of the disease, was not found to be MHC or Ig heavy chain allotype linked. F1 hybrids between a resistant strain and two of the susceptible strains were found to be resistant to the induction of the disease, indicating that susceptibility is inherited as a recessive trait. In the autoimmune NZB/W F1 female mice, immunization with the 16/6 Id resulted in an early onset of the SLE-like disease. The results of the present study indicate the role of the anti-16/6 Id antibodies in the induction of experimental SLE, and provide direct evidence for the importance of the genetic background in determining susceptibility to SLE.

Animals↗
PubMed1990

Sex hormone involvement in the induction of experimental systemic lupus erythematosus by a pathogenic anti-DNA idiotype in naive mice.

The effect of sex hormones on the induction of experimental systemic lupus erythematosus (SLE) with a human anti-DNA (16/6 Id +) antibody, was studied. We found that injection of the pathogenic idiotype to BALB/c females and orchiectomized males treated with estrogen caused a rapid outburst of the disease 3 months after immunization, while nonestrogen treated mice developed the disease 5 months after immunization. The flare of SLE disease was characterized by raised levels of autoantibodies in the sera to dsDNA, histones, cardiolipin, Sm, RNP, SSA (Ro), SSB (La) and an emergence of high titers of mouse antibody carrying the 16/6 Id. These enhanced antibody levels were associated with an increase in erythrocyte sedimentation rate, proteinuria and leukopenia. Immunofluorescent studies confirmed the existence of immune complexes in the afflicted kidneys. Testosterone treated BALB/c females and orchiectomized males developed a classical response to the human anti-DNA antibody (16/6 Id +), but failed to develop fulminant SLE-like disease. Our data demonstrate the importance of sex hormones on the induction of experimental SLE-like disease in mice with no genetic tendency to autoimmunity.

Animals↗
PubMed1989

Direct binding of a myasthenia gravis related epitope to MHC class II molecules on living murine antigen-presenting cells.

MHC gene products present antigenic epitopes to the antigen receptor on T cells. Nevertheless, direct binding of such epitopes to MHC class II proteins on normal living antigen-presenting cells (APCs) has not yet been demonstrated. We have previously shown a significant difference in the ability of T cells of myasthenia gravis (MG) patients to proliferate in response to the synthetic peptide p195-212 of the human acetylcholine receptor (AChR) alpha-subunit in comparison to healthy controls. The observed proliferative responses correlated significantly with HLA-DR5. Moreover, lymph node cells of various mouse strains that were primed with the T cell epitope, p195-212, were found to proliferate to different extents. To investigate these observations further, we designed an assay for direct binding of p195-212 to MHC class II proteins on the surface of freshly prepared splenic adherent cells. Binding of a biotinylated p195-212 was monitored using phycoerythrin-avidin by flow cytometry. Fifteen to sixty per cent of the cells were labeled following incubation with the biotinylated peptide. Binding was observed only to splenic adherent cells derived from mouse strains of which T cells were capable of proliferating in response to p195-212. The binding specificity, in terms of epitope structure and its site of interaction on the cells, was shown by its inhibition with an excess of the unlabeled peptide or with the relevant monoclonal anti-I-A antibodies. These results constitute the first direct evidence for the specific binding of a T cell epitope to live APC.

Amino Acid Sequence↗
PubMed1989

Correlation between the biologic functions and the generation of lymphokines in T cell clones.

We have recently reported that various murine T cell clones produce IL-1. Based on this observation we have analyzed in the present study the correlation between the biological functions and the generation of different lymphokines in (T,G)-A--L specific CD4+ clones. One subset of clones--the "helper clones"--were found to provide help to primed B cells, in vitro. These cells could be shown to produce IL-1, IL-2, and B cell stimulatory factor 1 (IL-4) activities and to express mRNA encoding for these three cytokines. The second subset of clones, termed "proliferative clones", were unable to help B cells in vitro but expressed vigorous Ag-dependent proliferations. These cells did not express IL-1, IL-2, or IL-4 activities. They produced another lymphokine(s) which may be granulocyte-macrophage-CSF, or some other factor recognized by the HT2 cell line. This study further substantiates the link between T cell activities and lymphokine repertoire with a special emphasis on the potential role(s) of T cell-derived IL-1.

Animals↗