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  • B7-1  (2)
  • Key words TNFα  (1)
  • Rheumatoid factor  (1)
  • 1
    ISSN: 1437-160X
    Keywords: Rheumatoid factor ; lpr gene ; Cryoglobulin ; Immune complex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The autosomal recessive mutant gene, lpr (lymphoproliferation), produces a massive proliferation of T cells in autoimmune MRL mice. Since the MRL strain bearing the lpr mutation is the only strain that spontaneously develops high titers of rheumatoid factors (RF), we have investigated whether non-autoimmune mice (C57BL/6, C3H/HeJ and AKR) bearing the lpr gene could produce RF. Serum levels of RF activity were assessed by a new radioimmunoassay, in which serum samples pretreated with acetate buffer were incubated with 125I-mouse IgG and precipitated with 7% polyethylene glycol. The majority of serum from 4- to 6-month-old non-autoimmune strains of mice bearing the lpr gene exhibited significant RF activity, as did MRL-lpr/lpr mice. Sucrose density-gradient analysis has revealed that all the IgG RF activity was present in a form of immune complexes, sedimenting in the intermediate position (7–19S) and fully dissociable into 7S IgG under an acid condition. This indicates that the production of IgG RF does not require a particular background genome of the MRL strain. In addition, mice bearing the lpr mutation developed extremely large amounts of cryoglobulins, which paralleled the production of RF. Analysis of components of their cryoglobulins revealed a marked enrichment of IgG3 subclass as compared to other IgG subclasses and IgM. These results suggest that IgG3-containing immune complexes represent the major source of cryoglobulins occurring in mice bearing the lpr gene.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: TNFα ; B7-1 ; transgenic ; mouse ; diabetes ; autoimmunity ; lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary While transgenic mice expressing tumour necrosis factor-alpha under the control of the beta-cell-specific insulin promoter display a marked lymphocytic infiltration of the islets, they never develop insulin-dependent diabetes mellitus (IDDM). In striking contrast, “double” transgenic mice whose beta cells express both tumour necrosis factor-alpha as well as the co-stimulatory B7-1 molecule all develop IDDM at an early age. Further, administration of anti-CD8 but not anti-CD4 immunoglobulins prevents diabetes onset. These results indicate that while tumour necrosis factor-alpha induced lymphocytic infiltration is not sufficient to effect beta-cell destruction, locally co-stimulated islet-infiltrating CD8+ T lymphocytes could play a critical role in the development of IDDM.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words TNFα ; B7-1 ; transgenic ; mouse ; diabetes ; autoimmunity ; lymphocytes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary While transgenic mice expressing tumour necrosis factor-alpha under the control of the beta-cell-specific insulin promoter display a marked lymphocytic infiltration of the islets, they never develop insulin-dependent diabetes mellitus (IDDM). In striking contrast, “double” transgenic mice whose beta cells express both tumour necrosis factor-alpha as well as the co-stimulatory B7-1 molecule all develop IDDM at an early age. Further, administration of anti-CD8 but not anti-CD4 immunoglobulins prevents diabetes onset. These results indicate that while tumour necrosis factor-alpha induced lymphocytic infiltration is not sufficient to effect beta-cell destruction, locally co-stimulated islet-infiltrating CD8+ T lymphocytes could play a critical role in the development of IDDM. [Diabetologia (1994) 37: 1277–1279]
    Type of Medium: Electronic Resource
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