γσ Lymphocytes in endocrine autoimmunity: evidence of expansion in Graves' disease but not in type 1 diabetes

Abstract

SUMMARY Endocrine autoimmune disorders are mediated by T cell-dependent responses to organ-specific antigens, but the mechanisms initiating the process remain unknown. Lymphocytes whieh use the γδ heterodimer as T ceii receptor (TCR) for antigen constitute a distinct subset of T cells whose function remains elusive. In order to investigate their possible involvement in endocrine auloimmunity we have determined the proportion of γδ T cells in the peripheral biood of 23 patients with type 1 (insulin-dependent) diabetes mellitus (type-1 DM) and 30 patients with autoimmune thyrotoxicosis (Graves’ disease). T lymphocyte TCR expression was assessed by fluorescence-activated flow eytometry on peripheral blood mononuclear cells using MoAbs UCHTI (CD3), TCR 51 (γδ TCR), WT31 and βF1 (αβ TCR) and both the percentage of T cells expressing γδ and the ratio γδ/αβ were calculated. In the diabetie patients γδ cells were not significantly different from (he control group (7·7 ± 54%versus 8·0 ± 5·5%) of T eells, P NS). There was no relation between the proportion of γδ lymphoeytes and the presence ol’ islet cell antibodies (ICA) in the sera. The Graves’ patients showed a tendency towards a higher proportion of γδ T lymphocytes than the controls (γδ/αβ ratios: 0·095 ± 0·047 versus 0·063 ± 0·022, P= 0·03). In 14 Graves’ patients the number of γδ were measured in paired samples of peripheral and inlrathyroidal lymphocytes, demonstrating an expansion of γδ within the thyroid glands (0·21 ± 0·3 versus 0·095 ± 0·047, P= 0·032). Immunohistochemical studies showed that γδ celts were scattered among the predominant αβ lymphoeytes infiltrating the thyroid gland and that they aeeount for 10% of intraepitheliai lymphocytes. No relation was found between the increase of γδ lymphocytes and any clinieai features.