摘要:

Non obese diabetic (NOD) mice spontaneously develop thyroiditis in addition to diabetes. Mononuclear cells begin to infiltrate the thyroid of these animals in the first month of life. The expression of major histocompatibility complex (MHC) class II (la) antigens by cells in the thyroid from NOD mice of various ages with and without thyroiditis was examined. We found that only 1 of the 9 infiltrated thyroids from 18 8-33 day old NOD mice surveyed expressed MHC class II antigens. Therefore la antigen expression appears to be secondary to infiltration and does not initiate the autoimmune process. Fourteen of 17 (82.2%) infiltrated and 7 of 11 (63.6%) uninfiltrated thyroids from NOD mice aged 51-73 days contained cells expressing la antigens. Sixteen of 18 (88.9%) infiltrated and all 7 of the uninfiltrated thyroids from mice aged>89 days contained la positive cells. These MHC class II expressing cells included thyroid epithelial cells (TEC), as well as interstitial cells such as macrophages. la positive cells in the thyroid have the potential of presenting thyroid specific antigen to infiltrating T cells and thereby maintaining or potentiating thyroid autoimmune destruction. Macrophages were observed in thyroid tissue from 9 of 11 (81.8%) infiltrated and 12 of 15 (80%) uninfiltrated 8-33 day old NOD mice, thyroids from 11 of 16 (68.7%) infiltrated and 6 of 9 (66.7%) uninfiltrated 51-73 day old NOD mice, as well as 28 of 29 (96.5%) uninfiltrated and all 9 of the uninfiltrated thyroid from NOD mice aged>89 days. Thyroids from control age matched non autoimmune BALB/c mice were consistently la antigen negative while macrophages were seen in some of the animals aged>60 days.

ISSN:0891-6934    

DOI:10.3109/08916939409014653

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

An IgGl mAb 1G10 derived from an autoimmuneMRL/Mp-Ipr/Ipr (MRL/Ipr)mouse has previously been shown to induce IL-3, TNF-αand IL-6 production, and autocrine growth in an IL-3-dependent myeloid cell line, FDC-P2/185-4. In the present study, we have attempted to further define the molecular mechanism responsible for the IG10-induced activation of FDC-P2/185-4 cells. We have shown that 1G10 lacked anti-IgG1 rheumatoid factor activity, failing to generate self-associated immune complexes. Since 1G10 stimulated cells in an FcγR-dependent manner, it seems likely that cross-linking of a cell surface antigen and FcyR by 1G10 antibody is responsible for the stimulation of FDC-P2/185-4 cells. Among several mAb specific to surface antigens expressed on FDC-P2/185-4 cells (MHC class I, LFA-1, and FcγR), only a mAb specific to theáchain of LFA-la was able to induce the IL-3 and FcγR-dependent proliferation of FDC-P2/185-4 cells, similar to that induced by 1G10. Immunoprecipitation analysis revealed that 1G10 recognized a polypeptide with a molecular mass of 140 kilodaltons (pi40), which differed from FcγR and from LFA-láchain. These results suggest that cross-linking of not general but particular cell surface antigens and FcyR stimulates FDC-P2/185-4 cells to produce cytokines resulting in their proliferation.

ISSN:0891-6934    

DOI:10.3109/08916939409014654

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Autoantibodies against the nonhistone nucleosomal protein HMG-17 have been detected in a high percentage of ANA-positive patients with pauciarticular-onset JRA4. Here we report on the epitope mapping of the HMG-17 autoantigen with a set of overlapping and nested synthetic peptides spanning the entire amino acid sequence of the human HMG-17 protein. Competition ELISA experiments defined a proline and lysine rich octapeptide PKPEPKPK as the major epitope recognized by more than 70 % of the HMG-17 positive JRA sera. Point mutations introduced in the autoimmune peptide determined the amino acid residues important for autoantibody recognition. Computer based sequence comparison shows close homology between the HMG-17 autoimmune epitope and certain infectious organisms, supporting the possibility that molecular mimicry is an important factor in the etiology of JRA.

ISSN:0891-6934    

DOI:10.3109/08916939409014655

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

T lymphocytes are implicated in the pathogenesis of Type 1 (insulin dependent) diabetes. Activated T lymphocytes expressing IL-2 receptors are found at increased levels in the peripheral blood in the prediabetic period, at diagnosis and for several months after the onset of the disease, but their role in the pathogenesis of the disease is not known. We have used co-culture of peripheral blood lymphocytes with IL-2 alone to selectively generate T cell clones from thein vivoactivated T cell population, and examined the phenotype and antigen specificity of the clones derived. From 3 patients with newly-diagnosed Type 1 diabetes 184 clones were generated, the majority of which (39%) were CD4+TCRaβ+, whilst 31% were CD8+TCRαβ+. From 2 healthy control subjects 90 clones were obtained, of which 62% were CD4+TCRαβ+and 33% were CD8+TCRαβ+. Antigen specificity was examined in 46 clones from the patients and 44 from the control subjects in proliferation assays, using as antigens homogenate of human islets of Langerhans, human islet membrane preparation and human liver membrane preparation. Three clones (all CD4+TCRap+) from the patients, but none from the control subjects, proliferated in a dose dependent fashion in response to stimulation with human islet homogenate presented by autologous APCs, but to neither of the other autoantigen preparations. Our results demonstrate that a relatively high proportion (7%) of T lymphocytes activatedin vivorecognise human islet antigens, indicating that they may have a role in the pathogenesis of the disease.

ISSN:0891-6934    

DOI:10.3109/08916939409014656

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

The nonobese diabetic (NOD) mouse spontaneously develops insulin dependent diabetes mellitus. The disease is associated with a leucocytic infiltration of the pancreatic islets of Langerhans and it is believed that during the development of autoimmune diabetes, the insulin-secreting islet P-cells are destroyed by autoreactive T lymphocytes. We investigated the alteration of lymphocyte subsets in central and peripheral lymphoid organs of NOD female mice with increasing age beginning before the onset of insulitis and ending well after the onset of diabetes. The spleen, inguinal and pancreatic lymph nodes all increased in cell number, especially after the onset of insulitis (8 weeks), and all decreased after the onset of diabetes. Flow cytometric studies showed a widening of the visible side scatter profile of female NOD lymph node cells which coincided with the initiation of insulitis. Anti-CD4 and anti-CD8 double staining of thymocytes revealed a large increase in the double negative population and a corresponding decrease in the double positive population, but this occurred long after the onset of diabetes. Generally, there was an increase in the CD4 : CD8 ratio in the peripheral lymphoid organs during the onset of insulitis which was largely due to an increase in the CD4 T cell population while the ratio decreased after the onset of diabetes. In the spleen this was mostly due to an increase in CD8 T cells. The pancreatic lymph nodes, which theoretically might reflect what is happening in the pancreas, showed an unexpected decrease in overall cell number and a decrease in T-cells (especially CD4 T cells), while B cells were increased. Overall, it would appear that no single immunological parameter could be used to predict a prediabetic state.

ISSN:0891-6934    

DOI:10.3109/08916939409014657

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We have used the reverse transcriptase polymerase chain reaction (RT-PCR) technique to assess the expression of cytokine genes in various T cell subsets of autoimmune-prone mice. Our study confirmed the previously described features in lpr mice that IFN-γ, TNF-α, and TNF-βwere transcribed by various T cell subsets. We in this study demonstrated that double negative (DN) T cells, the major cell population in lpr mice, failed to express interleukin-3 (IL-3), IL-4, IL-5, and IL-6 genes that influence B cell growth and activation. In contrast, DN T cells expressed Eta-1 gene that is shown to augment polyclonal activation of B cells and immunoglobulin production. Thus, it is conceivable that T cell-derived B cell-stimulatory activities in MRL/lpr mice can be attributed to Eta-1, rather than IL-3, IL-4, IL-5 or IL-6. We also demonstrated that CD4+T cells infiltrating into kidney tissues of MRL/Ipr mice expressed various cytokine genes such as IL-1, IL-5, IL-6, IFN-γ, TNF-α, TNF-βand TGF-p.

ISSN:0891-6934    

DOI:10.3109/08916939409014658

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

HLA-DR positive cells infiltrating Graves' thyroid tissue were examined for their expression of cell-specific immunological markers using light and electron microscopic immunostaining of frozen sections and isolated open thyroid follicles. Graves' glands (n = 21) were enriched of CD68 and Leu-M5/CD1 lc positive monocytes/macrophages as well as CD4 and CD8 lymphocytes. These cell types were distributed juxtafollicular as well as in other tissue areas. Only the RFD-1 antibody, considered to label antigen-presenting cells including dendritic cells, identified cells invariably located close to the interstitial follicular surface. After follicle isolation, RFD-1 cells were enriched compared to Leu-M5 cells and exclusively adherent to the follicular epithelium. The plasma membrane of RFD-1 positive cells were in intimate contact with the basolateral membrane of the thyrocytes, sometimes extending deeply into the intercellular space of the epithelium. Parallel labelling experiments suggested that the follicle-adhering RFD-1 cells also expressed HLA-DR. Our findings show that in human thyroid glands with Graves' disease RFD-1 positive cells with a dendritic morphology establish direct contact with the follicular epithelium. In view of the fact that both HLA-DR and RFD-1 are associated with antigen-presenting functions it is suggested that a direct interaction of dendritic cells with thyrocytes might be an important component of the autoimmune reaction in Graves' disease.

ISSN:0891-6934    

DOI:10.3109/08916939409014659

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Natural or deliberate activation of the immune system of pathogen-free mice markedly affected their response to an autoimmune-inducing stimulus. Specifically, mice immunized with rat red blood cells were found to make antibodies reactive with both rat and mouse erythrocytes. Animals housed for an extended period in a conventional environment developed an autoimmune response twice as fast as those kept in isolators. In an attempt to emulate this effect, mice kept in a sterile environment were infected with a potent polyclonal activator of B lymphocytes, lactate dehydrogenase-elevating virus, at the same time as they were inoculated with rat erythrocytes. Whereas uninfected animals developed a progressively increasing autoantibody titer, infected mice quickly attained high anti-erythrocyte autoantibody titers that remained rather constant. Contrary to circulating autoantibodies, bound anti-erythrocyte antibodies decreased with time. Virus infection enhanced all the IgG subclass responses, with the exception of IgGl, to both rat and mouse erythrocytes. None of the modifications of the autoimmune responses resulted in anemia.

ISSN:0891-6934    

DOI:10.3109/08916939409014660

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939409014661

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939409014662

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor