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T-Cell Apoptosis in Inflammatory Neuromuscular Disorders Associated With Human Immunodeficiency Virus Infection
Christiane Schneider, MD;
Marinos C. Dalakas, MD;
Klaus V. Toyka, MD;
Gérard Said, MD;
Hans-Peter Hartung, MD;
Ralf Gold, MD
Arch Neurol. 1999;56:79-83.
Background Apoptosis is one of the major mechanisms of CD4+ T-cell depletion in human immunodeficiency virus (HIV) infection. T cells in human inflammatory myopathies in HIV-negative individuals rarely undergo apoptosis. Currently, there is no information available concerning the fate of T cells in HIV-associated myositis and polyneuropathies.
Objective To investigate whether apoptosis occurs in inflammatory lesions of muscle and nerve biopsy specimens of untreated HIV-positive patients with neuromuscular disorders.
Methods T-cell apoptosis was investigated in muscle and nerve specimens from 12 patients with HIV-associated polymyositis and 8 patients with HIV-associated inflammatory polyneuropathy. These were compared with specimens from 36 HIV-negative patients with other inflammatory myopathies and from 18 patients with inflammatory polyneuropathies. Apoptosis was assessed according to morphological criteria and with the use of in situ labeling methods.
Results In none of the HIV-associated disorders did we observe a substantial proportion of apoptotic T cells as assessed by nuclear morphological findings and in situ labeling techniques. Fas expression was up-regulated only in a few inflammatory cells. Positive labeling for Fas ligand was not associated with increased apoptosis of surrounding T cells. Nuclei of degenerating muscle fibers and macrophages did not show morphological signs of apoptosis and were not labeled by the tailing reaction.
Conclusions Similar to their idiopathic counterparts, in HIV-related polymyositis and inflammatory neuropathy, T-cell inflammation is not cleared by apoptosis. The observations are consistent with the non–self-limited nature of endomysial or endoneural inflammation and suggest that in HIV-positive patients, the T-cell elimination is differentially regulated in the lymphoid organs as compared with neuromuscular tissues.
From the Clinical Research Unit for Multiple Sclerosis, Department of Neurology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany (Drs Schneider, Toyka, Hartung, and Gold); National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md (Dr Dalakas); and Department of Neurology, Centre Hospitalier Universitaire de Bicêtre, Le Kremlin Bicêtre, Paris, France (Dr Said).
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