We analyzed frozen brain specimens from three patients with subacute sclerosing panencephalitis (SSPE) for the presence of interleukin (IL)-1 beta, IL-2, IL-6, tumor necrosis factor (TNF), lymphotoxin (LT), and interferon (IFN)-gamma using immunocytochemical techniques. We detected these cytokines in SSPE brain lesions demonstrating extensive cellular infiltrates, demyelination, and gliosis. Double-label immunocytochemistry, using cell-specific markers, showed that positive immunoreactivity for these cytokines was present on both infiltrating cells and resident brain cells. We also found IL-6, TNF, and IFN-gamma at lower levels in brain tissue from a patient with progressive multifocal leukoencephalopathy. In contrast, normal control brain sections showed no reactivity for any of the cytokines. These findings indicate that IL-1 beta, IL-2, IL-6, TNT, LT, and IFN-gamma may be produced in SSPE lesions and may be involved in the lesion pathogenesis of SSPE.
We examined the expression of Fas antigen and Bcl-2 protein in thymic tissue surgically resected from 10 patients with myasthenia gravis, using immunocytochemical techniques. Histologically, thymic tissues from 7 myasthenia gravis patients showed hyperplasia, while 3 other patients had thymomas. In hyperplastic thymic tissue, immunoreactivity for Fas antigen was observed mainly in the network of medullary epithelial cells. In contrast, expression of Fas antigen was rare in the cortex. Fas antigen was also detected to some degree in thymoma tissue from 3 patients. Bcl-2 protein was highly expressed in the medullary thymocytes in the hyperplastic thymic tissue, whereas its staining was quite low in myasthenia gravis thymomas. The number of Bcl-2-positive thymocytes in the medulla was significantly greater in the hyperplastic myasthenia gravis thymic tissue than in the control thymic tissue. These findings suggest that Bcl-2 protein may be upregulated in the myasthenia gravis thymus and that this phenomenon may be related to impaired apoptotic cell death of autoreactive thymocytes in myasthenia gravis.
OX40, expressed in a fraction of activated CD4+ T cells, may be upregulated in thymic tissues adjacent to GC and thymoma in MG, and OX40 may interact with OX40L in GC to enhance anti-acetylcholine receptor antibody production in MG.
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