摘要:

To investigate T-cell sensitization to thyroid autoantigens in autoimmune thyroid disease (AITD), purified soluble human thyroglobulin (Tg) and thyroid peroxidase (TPO) were used. Peripheral blood mononuclear cells (PBMC) as well as CD8-depleted, CD4-enriched PBMC (“selected”PBMC) from 9 patients with Graves' disease (GD). 13 Hashimoto's thyroiditis (HT) and 10 healthy subjects, were cultured for 6 days with or without varying concentrations (0.1, 1.0 and 5.0μg/ml. respectively) of Tg or TPO and their responses were evaluated using the3H-thymidine incorporation assay.Total PBMC as well as selected PBMC from GD and HT responded to both TPO and Tg, but normal PBMC did not. This induction was more marked in selected PBMC; on the other hand, CD8 depletion did not permit normal PBMC to respond to either antigen. However, reactivity of selected AITD PBMC to Tg differed from that of TPO. Two way analysis of variance showed that the proliferative response was significantly greater with Tg than with TPO, (again particularly notable with the“selected”PBMC) in both GD and HT. There was no difference between control and AITD preparations when an irrelevant (renal microsomal) antigen was employed. Taken together with our previous report that CD4 cells were induced by TPO even when cultured with CD8 cells, it is evident that suppressor CD8 cells do play a role in CD4 cells from proliferating against Tg and TPO however their function alone or in combination with suppressor-inducer CD4 cells is partially disturbed. so that T cell sensitization to Tg and TPO can be identified in the AITD PBMC.

ISSN:0891-6934    

DOI:10.3109/08916939309079227

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Relative reactivity of anti-lymphocyte autoantibodies (ALA) from patients with systemic lupus erythematosus (SLE) against CD4+ and CD8+ T cells was studied using C'-dependent microcytotoxicity assay. Of 46 SLE sera screened for anti-T cell autoantibodies, 27 sera (59%) showed significant cytotoxic reactivity. Of these, positive correlation between the titer of anti-T cell antibody and CD4/CD8 killing ratio (p<0.01) was demonstrated. In time course study of individual patients, the CD4/CD8 killing ratio increased and decreased as the disease flared and subsided and was accompanied by parallel changes in the titer of anti-T cell antibody titer. Moreover, as sera were serially diluted, the CD4/CD8 killing ratio decreased in 5 out of 10 sera. These results suggest that discrepancy among reports concerning the subset specificity of anti-T cell antibodies may be due, in part. to differences in the titer of ALA in the sera studied and to the dilution of serum used.

ISSN:0891-6934    

DOI:10.3109/08916939309079228

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We analyzed morphologically autoimmune disease in MRL/MpJ mice bearing both theYaaand thelprgenes (MRL-lpr, Yaamice), and compared it with that in MRL/MpJ-lpr/lpr (MRL-lpr) mice, in order to examine the effect of theYaagene onlpr-induced tissue-specific immunopathologies. MRL-lpr, Yaamale mice developed glomerulonephritis more rapidly than did MRL-lprmales. The glomerular damage in MRL-lpr, Yaamales, as evaluated by histologic and immunofluorescent methods, was significantly greater than that in age-matched MRL-lprmales. In contrast, no differences in the development of vasculitis and arthritis were noted between the two groups. Pathological examination of the dead mice revealed a similar incidence of lethal glomerulonephritis in the two groups. Lymphoid hyperplasia in the spleen consisted predominantly of unusual T cells (B220+, Thy-1+, CD4−, CD8−) in the two groups, and an increased number of B cells was not found in MRL-lpr, Yaamice. The histological nature of the autoimmune diseases was similar in MRL-lpr, Yaaand MRL-lprmales. These results indicate that theYaagene accelerates the development of glomerulonephritis but not that of vasculitis or arthritis. suggesting that the mechanisms underlying the initiation of glomerulonephritis are different from those leading to vasculitis or arthritis in MRL-lprmice.

ISSN:0891-6934    

DOI:10.3109/08916939309079229

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Diabetes-prone BB/OK rats aged 30 to 35 days were subjected to three sequential intrasplenic injections of unfractionated homogenate prepared from Langerhans' islets of newborn syngeneic BB/OK rats. Syngeneic islet antigen administration resulted in increased complement-dependent antibody-mediated cytotoxicity (C'AMC) to rat pancreatic islet cells in serum, compared to buffer-treated control animals as detected by51Cr-release assay. However, the increase of anti-islet-cell cyto toxicity neither impaired glucose tolerance nor affected the incidence of diabetes and the age at manifestation. In contrast to BB/OK rats developing diabetes, animals remaining long-term normoglycaemic did not show an enhancement of cytotoxicity to islet cells within twelve days after the first islet antigen injection as revealed retrospectively.In conclusion, humoral mediated anti-islet-cell cytotoxicity is not decisively involved in pancreaticβ-cell destruction and promotion of diabetes development in BB/OK rats, but animals becoming diabetic seem to be characterized by a stronger immunological reactivity upon syngeneic islet antigen challenge as indicated by an increase of anti-islet C'AMC compared to long-term normoglycaemic rats.

ISSN:0891-6934    

DOI:10.3109/08916939309079230

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

BUF/Mna rats develop spontaneous thymomas in an autosomal dominant manner. We constructed recombinant plasmid library of 90 and 185 base-paired (bp) satellite I DNA fragments isolated from BUF/Mna rat thymoma DNA. Four unusual clones containing 93, 95, 95, and 173 bp inserts were isolated by colony hybridization with Wistar rat satellite I DNA. Nucleotide sequence analysis of the inserts of the 4 clones revealed abnormal sequence organization and unusual subunit structure of the rat satellite I DNA. Sequence comparisons between normal and abnormal satellite I DNA suggested that the unusual subunit structure could be generated by the change of the Hinf I recognition sequence to an Eco RI cleavage site, in addition to random deletions, insertions and base substitutions. The heptanucleotide sequence TGGGAAC, which is strictly conserved in normal subunits, was completely lost in all these clones. Southern blot hybridization revealed the amplification of abnormal satellite I DNA in BUF/Mna rat thymomas.

ISSN:0891-6934    

DOI:10.3109/08916939309079231

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Auto antibodies to anterior pituitary ACTH cells have been described in the sera from patients with Cushing's disease. We were here able to show that true ACTH cell auto antibodies do not react with the hormone itself or with Fc receptors in ACTH cells. They rather recognize a distinct pituitary cell-specific cytoplasmatic auto antigen located in a juxtanuclear position. ACTH cells from human adult pituitaries express Fc receptors producing a non-specific broad and diffuse cytoplasmic binding of normal immunoglobulins. After preparation of Fc-free F(ab)2fractions from human immunoglobulins it could be demonstrated by immunohistochemical methods that human adult pituitary ACTH cells also contain the fetal ACTH cell auto antigen. However, Fc receptors, ACTH hormone or other proopiomelanocortin- (POMC-) derived fragments and the ACTH cell auto antigen are all located at distinct intracellular sites. ACTH cells in human fetal pituitaries were shown to lack Fc receptors. Thus, with this source of antigen the characteristic auto antibody pattern can be detected with undigested sera.

ISSN:0891-6934    

DOI:10.3109/08916939309079232

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

In human immune deficiency virus (HIV) disease, direct infection of heart tissue with HIV and repeated intestinal infections with opportunistic pathogens are thought to be the main cause of cardiac disease and diarrhoea respectively. A role for autoimmune phenomena may also be involved in the pathogeny of HIV disease. In this study, we demonstrate that immunoglobulins from the A and G classes from HIV positive patients are able to interfere with the function of the muscarinic cholinergic receptors from heart and gut. Both IgA and IgG HIV+ preparations decreased the tension of isolated atria and increased the tension of isolated ileum. The mechanical effect of carbachol was inhibited in both atria and ileum preparations. when they were preincubated with either IgA or IgG HIV+ fractions.An inhibitor of muscarinic cholinergic receptors (atropine) impaired the negative inotropic action of HIV+ immunoglobulins (Ig) on the heart and prevented the positive inotropic effect of HIV+ Igs on ileum.HIV+ IgA fraction was approximately ten fold more potent to interfere with the cholinergic function as compared to the IgG fraction.These results suggest that antibodies present in HIV+ serum may also modulate muscle's cholinergic activity in the heart and ileum from HIV+ patients.

ISSN:0891-6934    

DOI:10.3109/08916939309079233

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

A cDNA encoding the extracellular domain of human TSHr (ETSHr) was expressed in large quantities using the baculovirus expression system. Maximum level of protein was produced at 60 hr post-infection and represented approximately 20% of the total cellular protein. The identity of the protein as ETSHr was confirmed by Western blot using antibodies to synthetic peptides derived from the TSHr. The protein has an apparent molecular weight of 50 kDa and is larger than the predicted size of 44 ma, suggesting that the protein is glycosylated. Polyclonal antibodies raised in rabbits against gel purified ETSHr blocked the binding of125I-TSH to native TSHr in solubilized porcine thyroid membranes in a radioreceptor assay. The availability of this antigenically active protein will facilitate further characterization of the protein and analysis of immune response against TSHr in experimental animals as well as in patients with autoimmune Graves' disease.

ISSN:0891-6934    

DOI:10.3109/08916939309079234

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Mice homozygous for the lymphoproliferation (lpr) gene spontaneously develop autoimmune syndrome. These mice were characterized by the massive accumulation of double negative (DN) T cells. Although peripheral T cells in normal mice do not express J11d antigen, those abnormal DN T cells in autoimmune-prone mice express J11d antigen. In this study, the mechanisms that control the expression of J11d antigen are analyzed. High concentration of calcium ionophore alone induces the expression of J11d antigen, but not of CD4. CDS, and activation antigens such as interleukin 2 receptor as well as transfemn receptor by J11d−DN T cells from lpr mice. The expression of J11d antigen is primarily regulated at the transcription level rather than the post transcription level. Experiments using metabolic inhibitors reveal that the induction of J11d antigen requires the activation of not only a Ca2+/calmodulin- but also protein kinase C-dependent signaling pathway. Furthermore, J11d−DN thymocytes from control mice share the similar functional property with DN lpr T cells in J11d antigen inducibility.

ISSN:0891-6934    

DOI:10.3109/08916939309079235

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

To investigate the factors regulating the entry of lymphocytes into the brain, we assessed the adhesionin vitroof51Cr labelled lymphocytes from peripheral blood of patients with multiple sclerosis (MS) to human cerebral endothelial cells, and evaluated the effect on the adhesion of endothelium activated by interferon-γ(IFN-γ). lipopolysaccharides (LPS), interleukin-1 (IL-1) and tumor necrosis factor (TNF). Patients with acute relapsing MS during an exacerbation showed significant increase in MNC adherence to cerebral. endothelial cells as compared with controls (p<0.001). MNC adherence to cerebral endothelial cells activated by IFN-γor LPS, was significantly increased as compared to the controls (p<0.01). MNC adherence to endothelial cells was not blocked by antibodies against the intercellular adhesion molecule-1 (ICAM-1), but was blocked by lymphocyte function-associated antigen-1 (LFA-1). The increased adherence observed in patients with acute relapsing MS during an exacerbation would modulate the migration of lymphocytes across the blood-brain barrier (BBB).

ISSN:0891-6934    

DOI:10.3109/08916939309079236

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor