Schwann cells and myasthenia gravis. Preferential uptake of soluble and membrane-bound AChR by normal and immortalized Schwann cells, and immunogenic presentation to AChR-specific T line lymphocytes.
The normal neuromuscular synapse is formed by the intimate association of nerve endings, postsynaptic end-plate foldings in the muscle fiber, and nonmyelinating Schwann cells (SC) sealing the synaptic ramifications. Because SC have been recognized recently to have an immunogenic potential inducible to present protein autoantigens to autoimmune T lymphocytes, and considering their close proximity to the acetylcholine receptor (AChR)-bearing postsynaptic membranes, presentation of soluble and membrane vesicle-bound AChR to appropriate T cells was investigated. Short-term monolayer cultures of SC isolated from neonatal rat sciatic nerves, as well as cells of an immortalized SC line of similar origin, were fully able to present the relevant molecular epitopes to major histocompatibility complex (MHC) compatible AChR-specific T line lymphocytes immunogenically. Presentation of AChR was restricted by RT1.B (I-A) MHC class II products. Both types of cultured rat SC were inducible to expression of MHC class I and II products, and they were able to phagocytose AChR-enriched membrane vesicles preferentially. In contrast, phagocytosis of latex particles by SC was negligible. These data qualify perisynaptic SC as potential presenter cells of autoimmunogenic AChR in myasthenia gravis. Thus, SC may play a critical and as-yet unpredicted regulatory role in the cellular pathogenesis of myasthenia gravis.
Max-Planck-Gesellschaft Clinical Research Unit for Multiple Sclerosis, Würzburg, Federal Republic of Germany.
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D000818:Animals; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000494:pharmacology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D009157:Myasthenia Gravis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D012583:Schwann Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure
D000939:Epitopes; D011950:Receptors, Cholinergic; D007371:Interferon-gamma