The production of
interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells (PBMC), CD4 cells, or CD8 cells in response to
interleukin-2 (IL-2) stimulation has been studied; the samples were obtained from 12 healthy control subjects, 19 patients with
Graves' disease (10
hyperthyroid and nine euthyroid), 13 patients with Hashimoto's
thyroiditis (four hypothyroid and nine euthyroid), and 15 patients with
rheumatoid arthritis (11 active and four inactive). A dose of
IL-2 (25 U/ml) was utilized to induce IFN-gamma by PBMC from all four groups. The incremental increase in IFN-gamma values (with IL-2 stimulation minus without stimulation) was significantly less in PBMC from patients with
Graves' disease, Hashimoto's
thyroiditis, and
rheumatoid arthritis than that in PBMC from control subjects. The values from PBMC in patients with
Graves' disease in a euthyroid state were below normal but greater than those from patients with
Graves' disease in a
hyperthyroid state. The incremental increase in IFN-gamma values from
Graves' disease PBMC correlated with the serum TSH values (r = 0.622, P less than 0.01), but not with thyroid
autoantibodies (anti-
thyroid microsomal antibodies, anti-
thyroid microsomal antibodies, nor
TSH-binding inhibitory immunoglobulin activities). The incremental increase in IFN-gamma from PBMC from both control subjects and
Graves' disease was correlated with that from CD4 cells (r = 0.711, P less than 0.01), but not with that from CD8 cells. The production of IFN-gamma in response to
IL-2 from PBMC in
Graves' disease correlated inversely with thyroid function, appearing to reflect the very effect of
hyperthyroidism in this process. The precise explanation of these phenomena remains unclear. The decreased response of IFN-gamma to
IL-2 stimulation by PBMC from patients with
Graves' disease, Hashimoto's
thyroiditis, and
rheumatoid arthritis seems to be a non-specific phenomenon occurring in both organ specific
autoimmune disease and systemic
autoimmune disease. It may be due to a down-regulation in
autoimmune disease of CD4 cells in response to
IL-2, a decreased level of
IL-2 cellular receptors or a decreased receptor affinity, associated increased soluble
IL-2 receptors, or a defect of the intra-CD4 cellular
IL-2 signal to produce or release IFN-gamma in the conditions studied.