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Autoimmune human T lymphocytes specific for acetylcholine receptor
Nature
|July 19, 1984
Summary
Researchers identified autoreactive T cells in patients with myasthenia gravis, suggesting a T-lymphocyte defect in this autoimmune disorder. A specific T-cell line, reactive to acetylcholine receptors (AChR), was established and linked to HLA-DR3.
Area of Science:
- Immunology
- Autoimmune Diseases
- Neuroimmunology
Background:
- Myasthenia gravis is a well-characterized autoimmune disorder.
- Autoantibodies to the nicotinic acetylcholine receptor (AChR) are key in its pathogenesis.
- Evidence suggests a role for thymus-dependent (T) lymphocytes in the underlying immunoregulation defect.
Purpose of the Study:
- To investigate the role of T lymphocytes in myasthenia gravis.
- To isolate and characterize autoreactive T cells in patients with myasthenia gravis.
Main Methods:
- Isolation of autoreactive T cells from six myasthenia gravis patients.
- Establishment of a long-term T-cell line from a patient homozygous for HLA-DR3.
- Characterization of T-cell line specificity, phenotype, and genetic restriction.
Main Results:
- Autoreactive T cells specific for acetylcholine receptors (AChR) were isolated.
- A T-cell line specific for fish and human AChR was established.
- The T-cell line exhibited an inducer/helper T-cell phenotype and was restricted to HLA-DR3.
- AChR-induced proliferation was inhibited by anti-DR monoclonal antibodies and DR3-specific antiserum.
Conclusions:
- These findings support a defect in T-lymphocyte immunoregulation in myasthenia gravis.
- Autoreactive T cells targeting AChR are implicated in the disease.
- The genetic restriction to HLA-DR3 highlights the role of specific MHC molecules in myasthenia gravis pathogenesis.