摘要:

CD5+B lymphocytes and TCR gamma-delta T lymphocytes, phenotypes implicated in the pathogenesis of autoimmune disease, were isolated from the vitreous in a case of acute sympathetic ophthalmitis. These cells were obtained using a method which allows the selective maintainance in vitro of in vivo activated T lymphocytes. Dual colour flow cytometry showed that after 3 days culture in IL-2 containing medium 61 % of cells were CD5/CD19 + ve and 41 % CD3/ TCR gamma delta + ve. Of the total CD3 + ve population, 15% were gamma/delta negative. These cells formed a population which also responded in a proliferation assay to retinal antigens. Histologically the eye showed a marked mononuclear cell infiltration of the retina, ciliary body and choroid. Granulomatous lesions within the choroid contained lymphocytes, plasma cells and multinucleate giant cells. Immunocytochemistry showed lymphocyte populations to be predominantly CD2 + ve CD3+ve T lymphocytes of the CD4 sub-set. Distribution of monocytes/macrophages throughout the lesions and restriction of B-lymphocytes to granulomata were all consistent with a DTH type reaction. Despite immunosuppressive therapy, the expression of activation antigens HLA-DR and ICAM-1 on infiltrating and resident ocular tissue cells was high, although IL-2 receptor (CD25) expression was virtually absent. Flow cytometric analysis of peripheral blood cells prior to treatment with Cyclosporin-A showed systemic activation of lymphocytes, with high levels of HLA-DR and CD25 expression and a raised CD4/CD8 ratio.

ISSN:0891-6934    

DOI:10.3109/08916939309115747

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Adjuvant-induced arthritis (AIA) can be passively transferred in Dark Agouti (DA) rats by spleen and lymph node cells after culture with Concanavalin A (Con A). A model not requiringin vitroCon A expansion and activation would be important in investigations of anti-rheumatic drugs in AIA. A new model using irradiated recipients fills this need. Donor DA rats treated with 0.1 ml complete Freund's adjuvant (CFA) containing 7.5 mgM. butyricum/ml were sacrificed 11 days after CFA injection, donor spleen cells harvested, and donor spleen cells injected intravenously into recipient DA rats previously irradiated with 5 Gy. Recipient rats developed arthritis 4-14 days after spleen cell transfer. This model can now be used to further define the effects of anti-rheumatic drugs in the passive transfer of AIA by eliminating the need for thein vitroCon A-induced expansion and/or activation of donor cells.

ISSN:0891-6934    

DOI:10.3109/08916939309115748

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The cDNAs coding for human full-length and soluble thyroid peroxidase (TPO) were constructed, cloned into a baculovirus transfer vector and used for infection ofSpodoptera frugiperda(Sf9) cells. The soluble TPO lacking 87 amino acids of the C-terminal transmembrane and intracisternal domains was designed as a fusion protein with a histidine-hexapeptide as an affinity ligand at its C-terminus. Whereas the recombinant full-length TPO was expressed mainly in an insoluble form in Sf9 cells, the recombinant soluble TPO was almost completely secreted into the culture medium. Both the full-length and the soluble TPO were purified by convential methods and by a specific affinity chromatography using metal chelating matrix respectively, and tested for their autoantigenicity towards anti-TPO autoantibodies. The ELISA established with the purified recombinant soluble TPO as antigen demonstrated its specificity, practicability and reproducibility in screening of anti-TPO autoantibodies in sera of autoimmune thyroid patients. High correlation (r = 0.89, n= 175) was obtained between the soluble TPO and natural TPO prepared from human thyroid glands. Pathological sera (n = 200) were positively assayed with a significance of 91%.

ISSN:0891-6934    

DOI:10.3109/08916939309115749

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Graves' disease is characterized by hyperthyroidism leading to enhanced production of thyroid hormones. Hyperthyroidism is primarily mediated by the binding of autoantibodies to the thyrotropin receptor (TSHr). In the past, either thyroid cells or thyroid membranes were used as a source of TSHr to detect anti-TSHr antibodies. Recently, we expressed the extracellular domain of the human TSHr (ETSHr) using the baculovirus expression system. In this study, we used ETSHr protein in an ELISA to detect anti-TSHr antibodies. Our data show that this assay can be used to analyze and quantitate isotype specific antibodies against the TSHr.To map immunogenic epitopes on the TSHr, we tested patients sera against synthetic peptides derived from two highly immunogenic regions (amino acid, AA 12-46 and 316-397) of the receptor. Although sera from patients with Graves' disease reacted with several peptides, they showed particularly strong reactivity against peptides from a relatively narrow region (i.e. AA 352-394) of the TSHr. The present study demonstrates the usefulness of the recombinant ETSHr to detect and characterize anti-TSHr antibodies in a simple and sensitive ELISA, and has lead to the identification of some of the immuno-reactive epitopes on the TSHr.

ISSN:0891-6934    

DOI:10.3109/08916939309115750

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939309115751

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Monocyte stimulation may be induced by various agents. Monocytes generate procoagulant activity (PCA) in response to stimulation; they widely interact with the hemostatic system and participate in thrombin formation. Extensive placental thrombotic infarction has been implicated in fetal death in poly abortive patients with lupus anticoagulant (LA).We investigated 38 polyabortive women: 17 LA negative (LA-) and 18 LA positive (LA+). We compared the results with 25 clinically normal women.After four hours of incubation, the mean value of monocyte PCA in the LA+ women was significantly higher than in either the LA- or the control group (p<0.0001). The monocyte PCA was out of the range of the controls in 9 of the 18 LA+ women.No correlation was observed between the levels of LA and monocyte PCA (r= 0.02;p= 0.94).No differences were found in monocyte PCA increase when induced by LA-, LA+ or control plasma; in all cases the increase was about five-six fold.Our results indicate that an increased monocyte PCA is present in some LA+ polyabortive women, thus suggesting that monocyte activation might be involved in the formation of thrombotic placental infarction and the consequent fetal loss in some patients. It might also suggest that these patients, in particular, could benefit from corticosteroid treatment, which is known to inhibit the formation of monocyte PCA.

ISSN:0891-6934    

DOI:10.3109/08916939309115752

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Islet cell antibodies (ICAs) in Chinese (23 IDDM, 13 NIDDM and 6 non-diabetic) were characterized for immunoglobulin isotypes and light chain specificity. All ICAs were IgG-type and none were IgM-or IgA-type (median titre: 20 JDF units; range 10-160). Light chain specificity showed that 25/36 (69.4%) of the diabetic patients had lambda and kappa chains. Half of the non-diabetic subjects had both lambda and kappa chains. The rest had only lambda chains. Isotyping for ICA-IgG subclass combination with IUIS/WHO reference monoclonal antibodies in the diabetic patients gave the following: IgG1, alone - 9 (25%), IgG1+2+3- 8 (22.2%), IgG1+2- 11 (30.6%), IgG1+3- 6 (16.7%), IgG2+3-2 (5.6%). No ICA-IgG4was detected. The frequency of the subclasses would be: IgG1, - 94.4%, IgG2- 58.3% and IgG3- 44.4%. The distribution of ICA-IgG subclasses was not affected by diabetes type (IDDM or NIDDM) or duration of disease. Of the 6 non-diabetic subjects only one had a single ICA-IgG subclass (IgG1,). Serum levels of IgG subclasses in a subgroup of the patients (n = 16) were not significantly different from normal individuals. Biochemical modification of pancreatic tissue prior to ICA testing showed that acetylneuraminic acid residues, lipid and protein components were associated with binding of ICAs. The co-existence of other autoantibodies was also tested in these 42 ICA-positive sera. Twelve individuals (1 non-diabetic) had thyroid autoantibodies. Antibodies to thyrotrophin receptor, gastric parietal cell and rheumatoid factor were not detected. These results indicate that ICAs in Chinese are not associated with IgG1subclass restriction, but are polyclonal in nature and require acetylneuraminic acid residues, lipid and protein components for binding.

ISSN:0891-6934    

DOI:10.3109/08916939309115753

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

It has been suggested that pancreaticβ-cell destruction occurring during the process leading to insulin-dependent diabetes mellitus (1DDM) involves formation of nitric oxide (NO). We have presently studied the effect of aminoguanidine (AG), which has recently been reported to inhibit generation of NO induced by the cytokine interleukin-1β. AG currently counteracted IL-1βinduced impairment of the glucose oxidation rate in rat pancreatic islets. Then we studied the effect of AG on the development of hyperglycemia and pancreatic insulitis in mice treated with multiple low dose injections of streptozotocin (40 mg/kg body-weight for five consecutive days). It was found that one daily intraperitoneal injection of AG (50 mg/kg body-weight) for 14 days failed to prevent the development of diabetes as well as insulitis following the streptozotocin injections. Furthermore, the mice treated with streptozotocin plus AG showed an increased mortality compared to mice treated with streptozotozin plus saline. Although the present data do not exclude a role for NO in IDDM, it raises concerns about the use of testing AG as therapeutic agent in IDDM.

ISSN:0891-6934    

DOI:10.3109/08916939309115754

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939309115755

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

In recent years there has been abundant interest in the properties and significance of the CD5+B cell subpopulation, fuelled by evidence that CD5+B cells play a central role in autoimmunity. Much of the current dogma about this cell subset is derived from studies in the mouse. On the basis of adoptive transfer experiments, murine CD5+B cells have been suggested to constitute a lineage distinct from“conventional”B cells, arising from progenitors which are present in fetal liver and omentum, but not in adult bone marrow. Moreover, a third lineage has been proposed, consisting of B cells which lack the CD5 antigen but which resemble in other respects CD5+B cells. These subpopulations are now termed Bla and Bib cells respectively, in contrast to the conventional B2 subpopulation. In their review, Kasaian and Casali discuss the role of human CD5+B cells in autoimmunity, and provide evidence for a subpopulation which lacks CD5 but can be distinguished by its lower than average expression of isoforms of leucocyte common antigen identified by CD45RA antibody. On the basis of their expression of CD5 mRNA and their apparent commitment to the production of natural antibodies, it is suggested that these may be the human equivalent of the mouse Bib cells.

ISSN:0891-6934    

DOI:10.3109/08916939309115756

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor