The distribution of peripheral blood CD16/56 cytotoxic T and natural killer (NK) cells in Graves' disease patients is analyzed in order to correlate them with disease activity and with prognosis. Eighteen patients with Graves' disease, twenty-four patients with Hashimoto's thyroiditis and thirtytwo sex-and age-matched healthy control subjects were studied. Peripheral blood CD16/56 (cytotoxic T and NK) cells were analyzed by cytofluorometry. A decreased proportion of CD16/56þ and CD16/ 56þCD3þ cells were detected in Graves' disease patients when compared with thyroiditis patients and healthy control groups. No correlation was detected with serum free thyroxine. On diagnosis, patients who would require a radical treatment for thyrotoxicosis control showed a significant decrease of cytotoxic CD56þ T (CD3þ) and NK (CD3¹) cells compared with those who would maintain the euthyroid state after methimazole. These results suggest that the cytotoxic compartment, both T and NK cells, of the immune system is altered in patients with Graves' disease, independently of the functional thyroid status. Changes in peripheral blood lymphocytes in Graves' disease patients could be useful as predictive markers of an unfavorable outcome.

SUMMARY The GR9 tumour was induced with methylcholanthrene in a BALB/c mouse, adapted to tissue culture and cloned without any passage in vivo. GR9 clones were typed for H‐2 with three monoclonal antibodies that define H‐2Kd+ Dd, Kd and Dd antigens. A great heterogeneity of H‐2d expression was found from clones which were Kd and Dd positive to clones Kd and Dd negative. These results were confirmed for A7 and B9 clones using immunoprecipitation with anti‐H‐2D.4 and anti‐H‐2K.31 alloantisera and SDS‐PAGE analysis. In addition, the number of chromosomes per cell was heterogeneous amongst the clones, ranging from 38 ± 2 to pseudotetraploid clones which have 75 ± 2 chromosomes. GR9 clones were injected into syngeneic BALB/c mice to measure local tumour growth. We found that the growth correlated with the amount of H‐2 antigen expressed, i.e. clones with low H‐2d expression were highly malignant while clones with normal H‐2d expression were highly immunogenic. Finally we found that BALB/c mice immunized against A7 (Kd, Dd‐positive) protected against A7, as expected, but surprisingly also against B9 (Kd, Dd‐negative).

In the present paper the distribution of peripheral blood T gamma/delta lymphocytes in Graves' disease patients is analyzed in order to correlate them with disease activity and with prognosis. Eighteen patients with Graves' disease, 24 patients with Hashimoto's thyroiditis and 32 sex- and age-matched healthy control subjects were studied. Peripheral blood CD3+ alpha/beta and gamma/delta T lymphocytes as well as CD4+ and CD8+ T cells, and CD19 (B) lymphocytes were analyzed by cytofluorometry. At diagnosis, patients who required a radical treatment for thyrotoxicosis control showed a significant decrease of T gamma/delta lymphocytes and an increase of B cells when compared with those who maintained the euthyroid state after methimazole. No correlation was detected between the percentages of these subpopulations and serum free thyroxine. This decreased proportion did not normalize after methimazole or radical treatments. These results suggest that the cytotoxic T gamma/delta compartment of the immune system is altered in patients with Graves' disease.

We have prospectively examined the percentage of peripheral blood lymphocytes which expressed adhesion molecules in untreated Graves' disease patients. Eighteen patients with Graves' disease, twenty-four patients with Hashimoto's thyroiditis and thirty-two sex-and age-matched healthy control subjects were studied. The expression of the lymphocyte adhesion molecules beta-1 integrin CD29, beta-2 integrin CD11b and L-selectin Leu8 (CD62L) was analyzed by cytofluorometry. A decreased percentage of CD29þ and CD11bþ lymphocytes was observed in hyperthyroid patients in comparison with Hashimoto's thyroiditis patients and healthy controls. However, there was no difference in the percentage of CD62Lþ lymphocytes in the three groups. Percentages of lymphocyte activation markers, hyperthyroid status, presence or absence of ophthalmopathy or serum levels of antithyroid antibodies were not related to the proportions of CD29þ or CD11bþ lymphocytes. Four Graves' patients required radical therapy but after the treatment, there was no modification in the percentages of CD29þ and CD11bþ lymphocytes compared with those determined at diagnosis. Our findings suggest that the decrease in beta-1 and beta-2 integrins could be a predisposing marker of development of Graves' disease.

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