摘要:

Administration of low doses of mercury induces autoantibodies to laminin and autoimmune glomerulonephropathy in BN, MAXX and DZB rats as well as in (BN×LEW)F1hybrids. LEW strain rats are resistant to these immunotoxic effects. Susceptible rats also show lymphoid hyperplasia in spleen and lymph nodes and severe thymic atrophy. It is still uncertain whether these mercury-induced changes have any role in the induction of autoimmune responses to laminin. In the present study, we have examined the effects of mercury on the thymus of susceptible and resistant rats. Histological analysis of thymuses from BN rats revealed extensive disorganization within 15 days following mercury treatment, with loss of demarcation between cortex and medulla. Numbers of thymus cells were significantly decreased in both BN and (BN×LEW)F1hybrid rats injected with HgCI2. There was no apparent increase in apoptotic cells in the thymus of these animals. By flow cytometry we detected a relative and absolute loss of double-positive CD4+CD8+thymocytes in BN (but not in LEW rats) within 15 days of mercury treatment. There was a corresponding increase in the relative proportion of single-positive (CD4+or CD8+) and double-negative CD4−CD8−thymocytes in mercury-treated BN rats. Absolute increases in the number of CD4+single-positive thymocytes were also observed. In contrast, mercury-treated LEW rats had no changes in thymus architecture or significant decreases in cell numbers. Since the thymus is important in both positive and negative selection of developing thymocytes, immunotoxic effects of mercury on its structure and thymocyte subpopulations may have multiple consequences. Alternatively, we suggest the hypothesis that autoimmunity (and in particular autoantibodies to laminin) may be responsible for the changes observed in the thymus.

ISSN:0891-6934    

DOI:10.3109/08916939608995331

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

It is disputed to what extent tumor necrosis factor-a is present in the thyroid follicular epithelial cells and/or in the interstitial cells in different disorders of the thyroid gland.We describe the immunohistochemical detection of tumor necrosis factor-αusing formaldehyde fixed and paraffin embedded tissue and a polyclonal anti-serum with high tumor necrosis factor-αneutralising activity. We examined the distribution of tumor necrosis factor-αin interstitial cells and follicular epithelial cells in thyroid carcinomas, adenomas, non-toxic multinodular goiters and autoimmune thyroid diseases.Tumor necrosis factor-αwas demonstrated in thyroid follicular epithelial cells, most frequently in non-toxic multinodular goiters (six of seven patients) and less frequently in adenomas (three of nine patients), papillary carcinomas (two of five patients), follicular carcinomas (one of five patients), Hashimoto's disease (one of six patients) and Graves' disease (one of seven patients). Tumor necrosis factor-αproducing interstitial cells were found in two thirds of patients with all six thyroid diseases.

ISSN:0891-6934    

DOI:10.3109/08916939608995332

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

In NOD mice, autoimmune recognition and destruction of pancreatic isletβ-cells appear to be independently regulated: all mice develop cellular infiltration of the islets (insulitis), but not all develop diabetes. The destructive potential of the insulitis lesion may depend on the balance between the two CD4+T-cell subsets, TH1 and TH2, that mediate cellular-cytotoxic and humoral responses, respectively. With a semiquantiative reverse transcriptase-PCR assay, we examined whether the disease process was reflected in the profiles of TH1 (IL-2, IFN-γand IL-12) and TH2 (IL-4, IL-6 and IL-10) cytokine mRNAs expressed in pancreata of NOD mice. Pancreata rather than isolated islets were examined to minimize manipulation ex vivo to preserve the expression of cytokine transcripts in vivo.At age 6 weeks, when 70% of mice had insulitis, all cytokine transcripts were detected in most pancreata, and their expression levels corresponded to the degree of insulitis. Similarly, during induction of diabetes with cyclophosphamide all transcripts were detected and levels corresponded with the degree of insulitis. In one-year-old mice without diabetes, all transcripts were detected but levels did not correspond to the degree of insulitis.Thus, in pancreata of NOD mice with different degrees of insulitis, we were unable to demonstrate, at the RNA level, polarisation of cytokine expression into either a TH1 or TH2 profile. This finding does not, however, exclude expression of distinct cytokine transcripts by immuno-inflammatory cells within the islet lesion, which might be revealed by in situ hybridization.

ISSN:0891-6934    

DOI:10.3109/08916939608995333

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

A possible association between the endogenous retrovirus, ERV3, and multiple sclerosis (MS) was exmined. Samples of DNA from 74 MS patients and 159 healthy blood donors were subjected to enzymatic amplification followed by single strand conformational analysis to detect polymorphisms in the long terminal repeats of ERV3. Using this approach we detected six single base pair variations and a drop-out of a nucleotide. The linkage pattern of these base pair variations enabled us to define three allelic forms of ERV3. Polymorphisms exclusively present in the group of patients were not found and the distribution of the three allelic forms did not differ significantly between the group of controls and the MS group. Neither was there a significant difference in the distribution of the three alleles between MS patients with the progressive form and patients with relapsing/remitting MS. Our results are not in support of an association between ERV3 and MS.

ISSN:0891-6934    

DOI:10.3109/08916939608995334

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Balkanic Nephropathy (BN) is characterized by: an incidence limited to a geographic area: a familial character and a slow progressive evoluation towards chronic renal failure associated with the symmetrical reduction of the kidney size. The etiology of BN is unknown.The aim of our study was to find out the immune alterations in BN pathology.In the BN patients we identified a novel subset of the CD3+CD 16+CD56+T cells expressing the phenotypic characteristics of both T lymphocytes and NK cells. The analysis of various subpopulations of lymphocytes, however, showed no quantitative differences in comparison with healthy subjects and healthy subjects from the endemic area.

ISSN:0891-6934    

DOI:10.3109/08916939608995335

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We have shown earlier that CD8 + T cell oligoclonality occurs frequently in normal individuals and generally exhibits a very diverse repertoire. In order to investigate the role of CD8 + T cells in MS, we analysed CD8 olgoclonality in 125 patients with MS in varying stages of disease. A multiplex PCR assay for CDR3 length variation was employed to detect oligoclonality in 25 TCRBV segments/families. CD8 clonal dominance was found to be frequent in MS. Comparison of the CD8 T cell repertoire in MS with that in normal controls revealed an increased frequency of oligoclonality involving the TCRBV9, - 18 and - 23 families. Sequence analysis of the TCRs from these clonally dominant CD8 + cells revealed a high degree of diversity overall. However, we observed one instance of identical TCRBV l8 sequences in CD 8 cells from two unrelated MS patients. In addition, several TCRs with motifs homologous to those found in MS brain and MBP specific T cell clones in EAE and MS were also detected. Future characterization of the function and specificity of these clonally expanded populations may provide insight into the nature of immune dysregulation in this autoimmune disorder.

ISSN:0891-6934    

DOI:10.3109/08916939608995336

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939608995337

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor