DIFFERENTIAL EXPRESSION OF PERFORIN IN MUSCLE-INFILTRATING T-CELLS INPOLYMYOSITIS AND DERMATOMYOSITIS

Polymyositis (PM) and dermatomyositis (DM) are the prototypical inflam matory diseases of skeletal muscle. In PM, CD8+ T cells invade and des troy muscle fibers, whereas humoral effector mechanisms prevail in DM, We studied the expression of the cytotoxic mediator perforin in infla mmatory cells in PM and DM muscle by semiquantitative PCR, immunohisto chemistry and confocal laser microscopy, Similar levels of perforin mR NA were expressed in PM and DM, and abundant perforin-expressing CD3+C D8+ and CD3+ CD4+ T cells were observed in both diseases, However, the re was a striking difference in the intracellular localization of perf orin. In DM, perforin was distributed randomly in the cytoplasm of the inflammatory T cells. In contrast, 43% of the CD8+ T cells that conta cted a muscle fiber in PM showed perforin located vectorially towards the target muscle fiber. The results suggest (a) that the random distr ibution of perforin in the cytoplasm of muscle-infiltrating T cells ob served in DM reflects nonspecific activation, and (b) that the vectori al orientation observed only in PM reflects the specific recognition v ia the T cell receptor of an antigen on the muscle fiber surface, poin ting to a perforin- and secretion-dependent mechanism of muscle fiber injury.