Expression and regulation of regulated on activation, normal T cells expressed and secreted in thyroid tissue of patients with graves' disease and thyroid autonomy and in thyroid-derived cell populations

Thyroid glands affected by Graves' disease (GD) show striking lymphocytic i nfiltration, mainly by CD45RO(+) T cells. The mechanisms by which the vario us lymphocytic subsets are recruited and maintained in the thyroid are unkn own. RANTES (regulated on activation, normal T cells expressed and secreted) in interaction with its receptors (CCR1, CCR3, CCR4 and CCR5) may be one of th e favorite chemokines involved in the cell trafficking and maintenance. RAN TES messenger RNA (mRNA) was quantified in the thyroid tissue of 16 patient s with GD and 7 patients with thyroid autonomy (TA), using competitive RT-P CR. We found a clear correlation between the RANTES mRNA level and 1) the d egree of T-cell infiltration (r = 0.68), and 2) the level of serum antibodi es to thyroid peroxidase (r = 0.76) in GD but not in TA patients. There was no difference between the autonomous nodules and the quiescent surrounding tissue in TA patients. To define the cellular source of RANTES mRNA and protein, we examined vario us thyroid-derived cells. Lymphocytes showed a markedly higher basal RANTES mRNA and protein level (mean +/- SEM; pg/mL, n = 3; 140 +/- 30) than thyro cytes (12 +/- 5) and fibroblasts (9 +/- 2). Lymphocyte stimulation with PMA enhanced RANTES secretion significantly(4490 +/- 200). Fibroblasts respond ed to stimulation with interleukin 1 (530 +/- 220) and turner necrosis fact or alpha (2780 +/- 1790), whereas thyrocytes did not. However, some thyroid carcinoma cell lines showed very high basal and stimulated RANTES expressi on. Lymphocytes expressed the mRNA of all chemokine receptors that bind RANTES. The number of CCR3(+) and CCR5(+) T cells was significantly higher in thyr oid-derived leukocytes than in those in the peripheral blood stream. We conclude that RANTES expression, mainly by lymphocytes, is perhaps invol ved in the maintenance of lymphocytic infiltration and, therefore, in the a utoimmune responses in GD.