APP-LYMPHOCYTES SELECTIVELY SORTED TO ENDOMYSIAL TUBES IN POLYMYOSITIS DISPLACE NCAM-EXPRESSING MUSCLE-FIBERS( T)

The characteristic pathogenic feature of polymyositis (PM) is muscle i nvasion by T lymphocytes penetrating the basal lamina and displacing t he sarcolemma of normal muscle fibers (T cell invasion of endomysial t ubes). Active forward movement of these T cells is indicated by cell e xtensions interdigitating with the muscle fiber surface. Here we descr ibe for the first time high abundance of Alzheimer amyloid protein pre cursor (APP) in invasive T cells contacting the border of muscle fiber s in PIM. These are the sites of muscle fiber displacement. The percen tage of APP(+) T cells at these sites is significantly higher than in other neuromuscular disorders with inflammatory infiltrates suggesting a specific pathogenic function of these cells in PIM. By using a new multiparameter immunofluorescence imaging procedure and confocal laser scanning microscopy, we show that APP(+) T cells in PM are invasive f ront cells that penetrate the basal lamina of the endomysial tube and displace the muscle fiber. Mononuclear cells behind the invasive front are negative for APP or show much lower APP levels. Front T cells eit her express the CD8(-)CD4(+)APP(+) or CD8(+)CD4(-)APP(+) phenotypes, o r are CD4(+)CD8(+)APP(+) T cell chimeras. The highest APP concentratio n is found at the tip of T normal by morphological criteria, the same fibers show intense staining for the regeneration marker NCAM. This re activity is highest at sites contacted by the APP(+) T cells. The find ings indicate that APP is specifically upregulated in T cells displaci ng muscle fibers in PM and suggest that NCAM, which mag be abnormally regulated in these fibers, is a candidate molecule for interaction wit h APP.