The effect of interleukin-2 on suppressor T lymphocytes in autoimmune thyroid disease

We have investigated the effects of interleukin-2 (IL-2) on the activation of suppressor T lymphocytes in autoimmune thyroid disease (AITD), with insulin-dependent diabetes mellitus (IDDM) as an autoimmune disease control; this was accomplished by measuring the expression of major histocompatibility complex class II (HLADR), CD25 (IL-2α receptor (R)), and IL-2βR expression on their surfaces by flow cytometric analysis. Peripheral blood mononuclear cells (PBMC), obtained from 10 patients with Graves' disease (GD), 11 with Hashimoto's thyroiditis (HT), 9 with insulin-dependent diabetes mellitus (IDDM), and 10 normal persons (N), were cultured for 7 d in the presence or absence of IL-2 at a final concentration of 50 U/mL. CD8⁺ cells were isolated from cultured PBMC with immunomagnetic beads, and were stained with fluorescent-conjugated monoclonal antibodies (anti-CD11b, anti-IL-2αR, anti-IL-2βR, and anti-HLA-DR); the activation of CD8⁺CD11b⁺ ('suppressor')T cells (Ts) by IL-2 was then analyzed on a flow cytometer. In the absence of IL-2, i.e., in the autologous mixed lymphocyte reaction (AMLR), Ts from patients with GD, HT, and IDDM showed significantly lower activation as compared to N when analyzed by HLA-DR expression, but were not significantly different when IL-2R expression was measured. We determined the Stimulation Index (SI) of the activation of T lymphocytes by IL-2 for comparison between N and patients. With stimulation of 50 U/mL of IL-2, SI of HLA-DR⁺ Ts was significantly (p < 0.05 to 0.01) lower in GD, HT, and IDDM as compared with N. There were no significant differences among autoimmune diseases (GD, HT, and IDDM); this signifies that reduced HLA-DR expression of Ts induced by IL-2 stimulation was not specific for AITD but was also seen in IDDM. The SI of HLA-DR⁺ Ts from GD correlated inversely with their serum T₃ levels (r = - 0.65, p < 0.05). On the other hand, the SI of IL-2-stimulated IL-2αR and IL-2βR expression of both N and patients' Ts were not significantly different. In conclusion, compared with N, AMLR reactivity and IL-2-induced activation of both AITD and IDDM Ts were significantly impaired when analyzed by HLA-DR expression but not significantly different by IL-2R expression, suggesting deficient or decreased transduction between IL-2R and HLA-DR expression on the cell surface of AITD and IDDM Ts. This may relate to a possible role of IL-2 as a nonspecific stimulatory factor in the pathogenesis of organ-specific autoimmune disease.