Cytolytic T Lymphocytes with Natural Killer Activity in Thyroid Infiltrate of Patients with Hashimoto's Thyroiditis: Analysis at Clonal Level*

Abstract

T Lymphocytes from thyroid infiltrates and peripheral blood (PB) of 3 patients with Hashimoto's thyroiditis (HT) were cloned using a microculture system previously shown to allow the clonal expansion of virtually all PB T lymphocytes from normal individuals. The phenotypic and functional features of a total number of 153 clones from thyroid infiltrates and 206 clones from PB were examined and compared with those of 272 clones derived from normal PB and spleens. The majority of clones derived from thyroid infiltrates of patients with HT had the cytotoxic/suppressor (T8+) phenotype, whereas the majority of clones from PB expressed the helper/inducer (T4+) phenotype. In addition, a consistent proportion (25%) of clones derived from PB of one patient had a phenotype (T3+T4-T8-) that was only occasionally found on clones obtained from PB or spleens of normal subjects. Most clones derived from both PB and thyroid infiltrates of the patients with HT had cytolytic activity, assessed by a lectin-dependent cytolytic assay against the murine P815 tumor cell line. The high frequency of cytotoxic T cells in thyroid infiltrates was related to the increased proportion of T8+ cells, whereas enhanced percentages of cytotoxic cell precursors with T4+ and T3+T4-T8- phenotypes primarily accounted for the high frequency of cytolytic T cells in the PB of the same patients. Many cytolytic T cell clones derived from thyroid infiltrates also had natural killer activity against human K562 and MOLT-4 target cells. These data provide the first functional analysis of T lymphocytes infiltrating the thyroid gland in patients with HT and suggest that the high proportions of cytolytic T cell precursors found in both thyroid infiltrates and PB of these patients may be of importance in determining the tissue damage in thyroid autoimmune disease.

New Ideas in Thyroid Autoimmunity

“…[Londei et al, in preparation]. Similar results have been recently published [15]. It is, however, significant that most antigen-specific cyto toxic T cells are CD8+ and recognise antigen in the context of MHC class I.…”

Clonal Analysis of T Lymphocytes Infiltrating the Thyroid Gland in Hashimoto’s Thyroiditis

“…The analysis of T cell clones is undergoing even wider applications in studying T cell function, and in deed it provides a very useful tool for investigating the functional repertoire of T cells from organ infil trates in patients with immunological or neoplastic diseases [11,19,20].…”

“…On the contrary, only a few studies have been con cerned with the clonal analysis of intrathyroid T cells [10][11][12], In the present work we cloned T cells infiltrat ing thyroid tissue in HT and analyzed the obtained clones for several functional capabilities (such as cy tolytic activities and lymphokine production). To this end, we applied a microculture system [13] that allows clonal expansion of virtually 100% peripheral blood (PB) normal T cells.…”

Suppression of peripheral blood natural killer cell activity by excess thyroid hormone.

“…Abbreviations used in this paper: E/T, effector/target ratio; IL-2, interleukin 2; LGL, large granular lymphocytes; LU, lytic units; NK, natural killer cells; PBL, peripheral blood lymphocytes; PHA, phytohemagglutinin; PTU, propylthiouracil; TSH, thyrotropin-stimulating hormone; T4, thyroxine. tolytic assay (6,7) or phenotypic marker (8)(9)(10). Perhaps in part due to the variety oftechniques used, there is a lack of uniformity of results and, specifically in hyperthyroidism, the cytolytic activity or concentration of peripheral blood NK/K cells has been reported as higher than normal (3), normal (8), or decreased (4,5,9).…”