MHC class I-mediated cytotoxicity does not induce apoptosis in muscle fibers nor in inflammatory T cells: studies in patients with polymyositis, dermatomyositis, and inclusion body myositis.
Apoptosis plays a crucial role in natural recovery from T cell-mediated autoimmune disorders of the nervous system. Whether apoptosis also occurs in human inflammatory myopathies is unclear. In this study we examined muscle biopsy specimens from untreated patients with polymyositis (n = 12), dermatomyositis (n = 12), and inclusion body myositis (n = 12) for the presence of apoptosis using morphological criteria and DNA fragmentation by in situ tailing. In all these disorders, only rare T cells exhibited signs of apoptosis by nuclear morphology and in situ labeling techniques. Although Fas-expression was upregulated in a few inflammatory cells, increased apoptosis of the surrounding T cells was not observed. Further, nuclei of degenerating muscle fibers did not show morphological signs of apoptosis and were not labeled by the tailing reaction. We conclude that in the inflammatory myopathies, T cell inflammation is not cleared by apoptosis and affected muscle fibers do not die by apoptosis. The observations are consistent with the non-self-limited nature of these disorders and suggest that, in contrast to the nervous system, the local microenvironment in muscle does not deliver pro-apoptotic stimuli.
Schneider
C
C
Department of Neurology, Julius-Maximilians-Universität Würzburg.
Gold
R
R
Dalakas
M C
MC
Schmied
M
M
Lassmann
H
H
Toyka
K V
KV
Hartung
H P
HP
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D003882:Dermatomyositis / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D017403:In Situ Hybridization; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000276:immunology*; D018979:Myositis, Inclusion Body / Q000276:immunology* / Q000473:pathology; D017285:Polymyositis / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019014:fas Receptor / Q000032:analysis
D015395:Histocompatibility Antigens Class I; D019014:fas Receptor