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

Norio Yoshikawa
Tetsuya Morita
Guillermo Arreaza
Erika Resetkova
Toshio Mukuta
Robert Volpé

Endocrinology Research Laboratory, Department of Medicine, The Wellesley Hospital, University of Toronto, Toronto, Ontario

(Original manuscript submitted 18/1/94; received in revised form 19/9/94; accepted 19/9/94)

Abstract

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 (HLA-DR), CD25 (IL-2alpha receptor (R)), and IL-2betaR expression on their surfaces by flow cytometric analyses. Peripheral blood mononuclear cells (PBMC), obtained from 10 patients with Graves' disease (GD), 11 with Hashimoto's thyroiditis (HT), 9 with 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-2alphaR, anti-IL-2betaR, and anti-HLA-DR); the activation of CD8+CD11b+ ("suppressor") T cells (Ts) by IL-2 was then analysed 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 analysed 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 T₃levels (r = -0.65, p < 0.05). On the other hand, the SI of IL-2-stimulated IL-2alphaR and IL-2betaR 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 analysed 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.

Clin Invest Med 1995; 18 (2): 91-98

Table of contents: CIM vol. 18, no. 2