Anti-thyroid drugs and lymphocyte function. II. The in vivo effect on blastogenesis and suppressor cell activity in Graves' disease

The proliferative response (PR) of T lymphocytes in PHA stimulated cultures (5 μg/ml and 0.5 μg/ml; 72 hr) was used to assess the suppressive capabilities of peripheral blood mononuclear cells (PBMC) in the thyrotoxic phase of Graves' disease and their possible modification by propylthiouracil (PTU) and methimazole (MMI) treatment. Graves' patients had 50% higher PR than controls. Treatment with PTU (n=6) for 9.5 weeks (mean) or MMI (n=6) for 18 weeks (mean) resulted in continuous decrease in PR, starting after 3 weeks and down to control values and plateau 7-10 weeks. This decrease correlated with the decline in plasma thyroxine (T4) levels which had already dropped by 3 weeks. Grouped according to thyroid functional state PR was significantly decreased only in the euthyroid state. Suppressor cell function, expressed as suppressor removal index (PR of PBMC pre-incubated for 24 hr/PR of fresh PBMC), was significantly lower in Graves' patients compared to controls and reached above normal values under PTU treatment: 0.98 ± 0.16, 1.39 ± and 1.94 ± 0.19 (mean ± S.E.M.) respectively. A direct suppressive effect of PTU in culture, observed in normal subjects, did not exist in untreated patients and evolved under MMI treatment to above normal levels. The cell-mediated PTU effect, exercised by PBMC pre-incubated with PTU treatment on autologous cells pre-incubated in medium alone, increased under PTU treatment to above normal levels. Both this cell-mediated suppressive effect and the augmented PR of pre-incubated cells were already significantly increased after 3 weeks of PTU treatment, when all patients were still thyrotoxic. We conclude therefore that PBMC of patients in the untreated, thyrotoxic phase of Graves' disease are deficient in an active cell-mediated suppressive function, a deficiency corrected - with compensatory overshoot - during anti-thyroid drug treatment.