Autoimmune human T lymphocytes specific for acetylcholine receptor

R Hohlfeld, KV Toyka, K Heininger, H Grosse-Wilde… - Nature, 1984 - nature.com
R Hohlfeld, KV Toyka, K Heininger, H Grosse-Wilde, I Kalies
Nature, 1984nature.com
Myasthenia gravis is one of the best characterized human autoimmune disorders1–4.
Circulating autoantibodies to the nicotinic acetylcholine receptor (AChR) at the
neuromuscular junction play a prominent part in the effector phase of the disease5, 6, but
little is known about the induction phase, that is, the immunoregulation. Indirect evidence,
such as thymic abnormalities7 and the association with certain histocompatibility antigens
(for example HLA-B8,-DR38, 9) suggests a defect of immunoregulation at the level of thymus …
Abstract
Myasthenia gravis is one of the best characterized human autoimmune disorders1–4. Circulating autoantibodies to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction play a prominent part in the effector phase of the disease5,6, but little is known about the induction phase, that is, the immunoregulation. Indirect evidence, such as thymic abnormalities7 and the association with certain histocompatibility antigens (for example HLA-B8,-DR38,9) suggests a defect of immunoregulation at the level of thymus-dependent (T) lymphocytes. We report here on the isolation of autoreactive T cells from six patients with myasthenia gravis. From one of these patients, who is homozygous for HLA-DR3, we established a long-term T-cell line. The line cells are specific for purified fish and human AChR, display the surface phenotype of inducer/helper T cells and are genetically restricted to HLA-DR3. AChR-induced proliferation could be inhibited with two monoclonal antibodies against monomorphic DR determinants and also with DR3-specific alloantiserum.
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