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-mediate d autoimmune disorders of the nervous system. Whether apoptosis also o ccurs in human inflammatory myopathies is unclear. In this study we ex amined muscle biopsy specimens from untreated patients with polymyosit is (n = 12), dermatomyositis (n = 12), and inclusion body myositis (n = 12) for the presence of apoptosis using morphological criteria and D NA fragmentation by in situ tailing. In all these disorders, only rare T cells exhibited signs of apoptosis by nuclear morphology and in sit u labeling techniques. Although Fas-expression was upregulated in a fe w inflammatory cells, increased apoptosis of the surrounding T cells w as not observed. Further, nuclei of degenerating muscle fibers did not show morphological signs of apoptosis and were not labeled by the tai ling reaction. We conclude that in the inflammatory myopathies, T cell inflammation is not cleared by apoptosis and affected muscle fibers d o not die by apoptosis. The observations are consistent with the non-s elf-limited nature of these disorders and suggest that, in contrast to the nervous system, the local microenvironment in muscle does not del iver pro-apoptotic stimuli.