摘要:

Although an autoimmune pathogenesis for non toxic goiter has been suggested, reports concerning circulating antibodies to TSH receptor structures have been conflicting. Intra thyroid lymphocytes, capable of secreting IgG, have been shown to be involved in the pathogenesis of Graves' and Hashimoto's diseases; therefore, the ability of conditioned media obtained from intra thyroid lymphocyte culture, and of IgG purified from these media, to stimulate cAMP accumulation and [3HI-Thymidine (TdR) uptake in FRTL-5 cells was investigated. The activity of IgG produced“in vitro”was compared with that of circulating IgG. Thyroid tissue samples were obtained at surgery from 21 patients with non toxic multinodular goiter (MNG), 5 patients with active Graves' disease (GD), and from 10 normal subjects, undergoing neck surgery for non-thyroidal pathology. IgG purified from media of GD lymphocyte cultures stimulated both cAMP accumulation and [3H]-TdR in 5 out of 5 cases: all of the IgG purified from control or MNG lymphocyte culture media was not active in either assay. Circulating IgG did not affect cAMP accumulation or [3H]-TdR in any of the non toxic MNG cases: controls showed no changed at all. However, both activities represented were increased by GD IgG. Conditioned media from intra thyroid lymphocyte cultures significantly inhibited basal cAMP accumulation in 7 out of the 21 non toxic MNG samples and totally abolished the response in all GD patients. [3H]-TdR was not affected by IgG of any of the controls, but it had an inhibitory effect on 8 out of 21 non toxic MNG patients, and significantly stimulated [HI-TdR in all GD patients. In conclusion, present data demonstrate that intra thyroid lymphocytes from non toxic MNG do not produce antibodies capable of mimicking TSH actions through the adenylate cyclase cascade. Conversely, soluble factors interacting in TSH-mediated functions of FRTL-5 cells are present in conditioned media of intra thyroid lymphocytes of GD and MNG thyroid lymphocytes of GD and MNG thyroid cultures.

ISSN:0891-6934    

DOI:10.3109/08916939008998416

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Several animal models of arthritis are produced using complete Freund's adjuvant (CFA) alone or with collagen as an arthritogen. Successful induction of arthritis is reported to require that the adjuvant mixture be administered by intradermal or subcutaneous routes. The resulting arthritis is caused by primarily cellular immune responses. Data presented in this paper show that giving CFA by intraperitoneal (I.P.) inoculation results in a humoral autoimmune response, with no obvious signs of arthritis. This humoral autoimmune response is characterized by production of autoantibodies to nuclear and cytoplasmic antigens, elevated levels of circulating immune complexes, and in approximately 25% of mice, rheumatoid factor.

ISSN:0891-6934    

DOI:10.3109/08916939008998417

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Cloned cDNA templates of thyroid peroxidase (TPO) have been used in conjunction with the polymerase chain reaction (PCR) to express selected segments of the thyroid microsomal/peroxidase antigen (TMA/ TPO) as recombinant protein inE. coli. Six small, different recombinant fragments averaging 120 amino acid residues and one large fragment (269 amino acids) of TPO which together encompass 80% of the extracellular region of the molecule have been produced and autoantibody (aAb) binding sites analysed by immunoblotting. A minimum of six independent, sequential antigenic determinants have been localized on the recombinant proteins and these map to the amino terminal, the central core region and the carboxyl terminal of the TPO molecule. More accurately, the six antigenic sites reside on overlapping recombinant TPO preparations termed Rla + Rlb (residues I to 160) Rlc (residues 145 to 250), R2b (residues 457 to 589). R3a (residues 577–677). R3b (residues 657–767) and R3c (residues 737–845). The large fragment of TPO termed R3 (residues 577–845) encompassing R3a, R3b and R3c also reacts with the aAbs. Different sera from patients with autoimmune thyroid disease contain antibodies to TMA/TPO which differ in their fine specificity. The use of recombinant molecular biological techniques together with PCR to prepare small segments of a large autoantigen as recombinant protein will now allow studies to progress on autoepitope mapping of the precise amino acid sequences of the TPO molecule with the use of synthetic peptides.

ISSN:0891-6934    

DOI:10.3109/08916939008998418

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

In this study we have correlated peripheral T cell subset phenotypes with intrathyroidal lymphocyte accumulation in patients with autoimmune thyroid disease (Graves' and Hashimoto's disease). Our study utilized euthyroid family members for one of our control groups (n= 48) thus significantly limiting familial, but not disease-specific, influences on these T cell phenotypes. Our principal new observations were found only in patients with Graves' disease. As previously reported, there was a decrease in CD8 f (suppressor/cytotoxic) T cells in the peripheral blood of patients with untreated hyperthyroid Graves' disease (n = 27) (mean±SEM, 19±1.1% in patients compared with 25±1.2% in controls,p= 0.03). a finding not observed in treated, euthyroid Graves' disease patients or their relatives. However, the relative number of CD8 + T cells, assessed by CD4CD8 ratios, was increased in the intrathyroidal T cell populations (n= lo), when compared to normal and patient peripheral blood. There were no consistent changes in total CD4f (helper) T cells in the peripheral blood of patients with treated and untreated Graves' disease but a reduction in CD4 + 2H4 + (suppressor-inducer) T cells was seen in patients undergoing surgery for Graves' disease (13±6.9% compared with 39±3.4%). Again, however, this T cell subset was increased within the target organ of the same patients (41±5.9%).These data point to either a selective accumulation, or a specific“homing”, of certain T cell subsets within the thyroid gland of patients with Graves' disease where T cell differentiation may be strongly influenced by antithyroid drug treatment and the local immune environment.

ISSN:0891-6934    

DOI:10.3109/08916939008998419

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Antinuclear antibodies, circulating immune complexes, rheumatoid factors and anticardiolipin antibodies were detected in the sera of 17 patients affected by the limited cutaneous subset of systemic sclerosis and marked clinical evidence of ischaemic cutaneous lesions (fingertip ulcerations). This study was designed to evaluate the possible role of anticardiolipin (aCL) antibodies and other immunological disorders in the endothelial damage characteristic of the disease. ACL antibodies were found in 41 % of the patients. With the exception of a significant connection with positive rheumatoid factor tests (RIA), no notable associations between anticardiolipin antibodies and antinuclear antibodies, circulating immune complexes (CIC), and other serological abnormalities were found.ACL antibodies did not significantly correlate with the presence of vascular lesions in our patients. However, a role of these antibodies in endothelial damage cannot be excluded, possibly in association with other serum factors such as immune complexes and antinuclear antibodies.A positive connection between the incidence of CIC and the severity of lung perfusion impairment was observed. and the previously reported relationship between anticentromere antibodies and calcinosis was indirectly confirmed.

ISSN:0891-6934    

DOI:10.3109/08916939008998420

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Studies presented here demonstrate the expression of the Ly-l gene and the detection of the Ly-l cytodifferentiation antigen in murine hybridomas producing autoantibodies. We examined the transcription of the Ly-I gene in thymocytes and 140 hybridomas producing autoantibodies of various specificities which were obtained from normal and autoimmune disease prone mouse strains. As previously demonstrated thymocytes stain brightly for Ly-l by immunofluorescence and express Ly-l transcripts. In our panel of hybridomas producing autoantibodies Ly-l transcripts were detected in 31 (45%) out of 69 NZB hybridomas and 7 (88%) out of 8 viable motheaten hybridomas. S1 nuclease protection experiments showed that Ly-l transcripts detected in thymocytes and B cells are the product of the same gene. The B cell transcripts are functional since immunofluorescence and Western data presented here detected the Ly-I protein in hybridomas cells which were found to transcribe the Ly-l gene. Interestingly a polymorphic transcription of the Ly-l gene was observed in B cells and B cell hybridomas as compared to thymocytes. Our results obtained in the hybridoma system firmly establish a major contribution of the Ly-l B cell subset to the production of DNA specific autoantibodies and a smaller contribution to the production of rheumatoid factors and“natural”, multispecific autoantibodies.

ISSN:0891-6934    

DOI:10.3109/08916939008998421

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Human isletβcells do not express HLA Class II normally, yet, in the diabetic pancreas,βcells are selectively positive for Class II and this may facilitate their recognition by T cells. It has been demonstrated that humanβcells can be induced to express Class II when cultured with IFN-γ+ TNF-αor IFN-γ+ TNF-β. To assess whether or not they can be induced to express the products of the Class II subregions, DR, DP and DQ, human islet cultures from 10 pancreases were supplemented with the combination of IFN-γ+ TNF-αusing MoAbs specific for DR, DP and DQ products, and antibodies to insulin and glucagon. The combination IFN-γ+ TNF-α(100–1000 U/ml each) was able to induce the expression of the three subregions in bothβandαcells. The induction of subregion expression followed the hierarchy DR>DQ⩾DP. The capability ofβcells to express all three Class II subregions supports the possibility that these cells can present their self antigens to T cells.

ISSN:0891-6934    

DOI:10.3109/08916939008998422

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939008998423

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939008998424

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor