Insoluble particulate antigen(s) in cell-mediated immunity of autoimmune thyroid disease

Cell-mediated immunity (CMI) in patients with Grave's disease, chronic thyroiditis, and primary hypothyroidism was observed by assay of lymphocyte-mediated cytotoxicity (LMC) and leukocyte migration inhibition (LMC). Lymphocyte responsivity to phytohemagglutinin (PHA) is normal in these disease. In the LMC assay, lymphocytes of patients in each category responded to the antigens of thyroid homogenates, but not purified human thyroglobulin. Cytotoxicity is least in Graves disease and most obvious in primary hypothyroidism. In the LMI assay, patients lymphocytes responded to thyroid microsomal--mitochondrial antigens, but not to thyroid cell sap. Lymphocytes of Graves disease patients also responded to liver microsomal mitochondrial antigens. The particulate antigens lost activity when solubilized by ultrasonication or KCL extraction. There is no correlation between the PHA responsivity of lymphocytes and thyroid function, or between CMI and serum antithyroid antibodies or thyroid size. Treated and untreated patients had similar evidence of CMI. These data indicate that function of thymus-derived lymphocyte in vitro is not disturbed in autommune thyroid disease and that CMI against thyroid antigens can be demonstrated by assay of LMC and LMI. Insoluble particulate antigens appear more important than soluble antigens in CMI. LMC, resumably induced by soluble cytotoxic factor, "lymphotoxin," may play an important role in the progress of the autoimmune thyroid disease to hypothyroidism.