THE EFFECT OF INTERLEUKIN-2 ON SUPPRESSOR T-LYMPHOCYTES IN AUTOIMMUNETHYROID-DISEASE

We have investigated the effects of interleukin-2 (IL-2) on the activa tion of suppressor T lymphocytes in autoimmune thyroid disease (AITD), with insulin-dependent diabetes mellitus (IDDM) as an autoimmune dise ase control; this was accomplished by measuring the expression of majo r histocompatibility complex class II (HLA-DR), CD25 (IL-2 alpha recep tor (R)), and IL-2 beta R expression on their surfaces by flow cytomet ric analysis. Peripheral blood mononuclear cells (PBMC), obtained from 10 patients with Graves' disease (GD), 11 with Hashimoto's thyroiditi s (HT), 9 with insulin-dependent diabetes mellitus (IDDM), and 10 norm al 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 fro m cultured PBMC with immunomagnetic beads, and were stained with fluor escent-conjugated monoclonal antibodies (anti-CD11b, anti-IL-2 alpha R , anti-IL-2 beta R, and anti-HLA-DR); the activation of CD8(+)CD11b(+) (''suppressor'') T cells (Ts) by IL-2 was then analyzed on a flow cyt ometer. In the absence of IL-2, i.e., in the autologous mixed lymphocy te reaction (AMLR), Ts from patients with GD, HT, and IDDM showed sign ificantly lower activation as compared to N when analyzed by HLA-DR ex pression, but were not significantly different when IL-2R expression w as measured. We determined the Stimulation Index (SI) of the activatio n 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, an d IDDM); this signifies that reduced HLA-DR expression of Ts induced b y 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 T-3 levels (r = -0.65, p < 0.05). On the other hand, the SI of IL-2-s timulated IL-2 alpha R and IL-2 beta R expression of both N and patien ts' Ts were not significantly different. In conclusion, compared with N, AMLR reactivity and IL-2-induced activation of both AITD and IDDM T s were significantly impaired when analyzed by HLA-DR expression but n ot significantly different by IL-2R expression, suggesting deficient o r decreased transduction between LL-2R and HLA-DR expression on the ce ll 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.