| 1. |
- Leijon, Kristina, 1967-, et al.
(author)
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Analysis of VH gene utilisation in the non-obese diabetic mouse
- 1993
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In: Autoimmunity. - : Harwood Academic. - 0891-6934 .- 1607-842X. ; 15:1, s. 11-18
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Journal article (peer-reviewed)abstract
- The immunoglobulin (Ig) heavy chain variable (VH) gene complexity and the VH gene utilisation pattern of the non-obese diabetic (NOD) mouse were investigated. We found that the NOD mouse displays a VH gene complexity which appears to be identical to that of the C57BL/6 mouse. Thus, Southern hybridisation using probes specific for 9 of the murine VH gene families revealed identical restriction fragment length polymorphism (RFLP) patterns in both mouse strains. As indicated by immunofluorescence analysis using allotype specific monoclonal antibodies the NOD mice were also found to carry the IgCH-1b allele. Collectively, these data suggest that the NOD mice carry an IgVH locus identical to that carried by C57BL/6. In contrast to the apparent identity at the level of germline VH gene repertoires, the pattern of VH gene utilisation differed considerably between these two mouse strains. Thus, in NOD mice the neonatal preference of D-proximal VH genes was found to be more pronounced than in C57BL/6 mice. Moreover, in contrast to adult C57BL/6 mice a D-proximal bias was evident also in adult NOD mice. On the basis of these findings we discuss the possibility that the distorted development of B cell repertoires in the NOD mouse could be directly or indirectly related to the T cell mediated, autoimmune process in the NOD mouse.
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| 2. |
- Mölne, Johan, 1958, et al.
(author)
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Adherence of RFD-1 positive dendritic cells to the basal surface of thyroid follicular cells in Graves' disease.
- 1994
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In: Autoimmunity. - 0891-6934. ; 17:1, s. 59-71
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Journal article (peer-reviewed)abstract
- 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/CD11c positive monocytes/macrophages as well as CD4 and CD8 lymphocytes. These cell types were distributed juxta-follicular 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.
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| 3. |
- Mölne, Johan, 1958, et al.
(author)
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Non-polarized cell surface expression of HLA-A,B,C and HLA-DR antigens in Graves' thyroid follicle cells.
- 1991
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In: Autoimmunity. - 0891-6934. ; 10:3, s. 189-99
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Journal article (peer-reviewed)abstract
- The intrathyroidal distribution and cell surface location of HLA-A,B,C and HLA-DR antigens was studied in polarized thyroid follicle cells from Graves' (n = 11) and normal (n = 3) thyroid tissue, using light and electron microscopy. Cryosections and isolated, open follicle segments were incubated with monoclonal antibodies against HLA-A,B,C and HLA-DR antigens and with patient sera containing autoantibodies against the microsomal antigen/thyroperoxidase. Immunoreactivity for HLA-A,B,C and HLA-DR on isolated thyroid follicle cells was frequently detected in Graves' disease, but absent in normal glands. There was a large variation in the immunolabelling between follicles as well as between different glands. Both HLA-A,B,C and HLA-DR immunoreactivity were detected on the apical and the basal surface of the follicle cells. Microsomal antigen/thyroperoxidase immunoreactivity was restricted to the apical cell surface. In contrast to normal tissue, HLA-DR positive cells with a dendritic or macrophage-like morphology were frequent in Graves' tissue. These cells adhered directly to the basal surface of isolated follicle segments. We conclude that HLA antigens are, unlike thyroid-specific plasma membrane constituents, expressed in a non-polarized manner at the surface of the follicular epithelium. These observations might have implications on the immune recognition of thyroidal autoantigens in Graves' disease.
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