title: Differential expression of perforin in muscle-infiltrating T cells in polymyositis and dermatomyositis.
abstract: Polymyositis (PM) and dermatomyositis (DM) are the prototypical inflammatory diseases of skeletal muscle. In PM, CD8+ T cells invade and destroy muscle fibers, whereas humoral effector mechanisms prevail in DM. We studied the expression of the cytotoxic mediator perforin in inflammatory cells in PM and DM muscle by semiquantitative PCR, immunohistochemistry and confocal laser microscopy. Similar levels of perforin mRNA were expressed in PM and DM, and abundant perforin-expressing CD3+CD8+ and CD3+ CD4+ T cells were observed in both diseases. However, there was a striking difference in the intracellular localization of perforin. In DM, perforin was distributed randomly in the cytoplasm of the inflammatory T cells. In contrast, 43% of the CD8+ T cells that contacted a muscle fiber in PM showed perforin located vectorially towards the target muscle fiber. The results suggest (a) that the random distribution of perforin in the cytoplasm of muscle-infiltrating T cells observed in DM reflects nonspecific activation, and (b) that the vectorial orientation observed only in PM reflects the specific recognition via the T cell receptor of an antigen on the muscle fiber surface, pointing to a perforin- and secretion-dependent mechanism of muscle fiber injury.
authors.affiliation: Department of Neuroimmunology, Max-Planck-Institute of Psychiatry, Martinsried, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Goebels
authors.forename: D
authors.initials: D
authors.lastname: Michaelis
authors.forename: M
authors.initials: M
authors.lastname: Engelhardt
authors.forename: S
authors.initials: S
authors.lastname: Huber
authors.forename: A
authors.initials: A
authors.lastname: Bender
authors.forename: D
authors.initials: D
authors.lastname: Pongratz
authors.forename: M A
authors.initials: MA
authors.lastname: Johnson
authors.forename: H
authors.initials: H
authors.lastname: Wekerle
authors.forename: J
authors.initials: J
authors.lastname: Tschopp
authors.forename: D
authors.initials: D
authors.lastname: Jenne
authors.forename: R
authors.initials: R
authors.lastname: Hohlfeld
mesh_terms: D001483:Base Sequence; D003882:Dermatomyositis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis*; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry* / Q000473:pathology; D054353:Perforin; D016133:Polymerase Chain Reaction; D017285:Polymyositis / Q000378:metabolism* / Q000473:pathology; D052899:Pore Forming Cytotoxic Proteins; D013601:T-Lymphocytes / Q000737:chemistry*
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin