Permanent Lines of T Lymphocytes Specific for Acetylcholine Receptors: A Clonal Approach to Study the Pathogenesis of Myasthenia Gravis
Myasthenia gravis is a disease of the neuromuscular synapse. Studies during the past decade have unequivocally established that the pathogenic defect in myasthenia is due to autoantibodies specific for the nicotinic acetylcholine receptors (AChR) of the end plate. These autoantibodies were demonstrated to bind to receptor bearing areas (1), they can transfer disease to formerly normal recipient animals (2), and cause accelerated receptor decay on the postsynaptic membranes (3). Humoral antibodies reflect, however, only one aspect of the autoimmune pathogenesis of myasthenia gravis. 1) There is strong evidence that, in addition, autoimmune T lymphocytes are critically involved in the pathogenesis of myasthenia gravis. This is most probably true in the afferent stages of the disease mechanism, and possibly also in the effector phase. The evidence for T cell participation in myasthenia gravis seems to be (loosely) linked to certain determinants of the human major histocompatibility gene complex, HLA (4). It is known that the immune response genes coded for within the major histocompatibility complex predominantly act in T cell dependent stages of the immune response (5). 2) Some, but possibly not all patients with myasthenia gravis possess peripheral blood lymphocytes reactive against isolated acetylcholine receptors by proliferation (6) or by secretion of lymphokines (7).
KeywordsAcetylcholine Receptor Cell Subline Mixed Leukocyte Culture Idiotypic Interaction Experimental Autoimmune Myasthenia
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