Self-reactive cytotoxic γδ T lymphocytes in Graves' disease specifically recognize thyroid epithelial cells

In this paper we report the isolation of a self-reactive cytotoxic γδ T cell line, 158RE.2, that originates from the T lymphocyte population infiltrating the thyroid gland of a patient with Graves' disease. Functional data using this cell line demonstrate that γδ T cells expanded in the thyroid tissue specifically recognize a ligand expressed by thyroid epithelial cells and cell lines of endocrine epithelial origin. The TCR expressed by these γδ T cells-Vγ1/Vδ5-is unusual in peripheral blood lymphocytes, and its specificity is clearly different from that observed in a high percentage of γδ T cells from PBL, which express the common TCR Vγ9/Vδ2. The Vγ1/Vδ5 receptor is involved in the recognition of the ligand expressed by the thyroid cells, but not in the NK-like activity also displayed by 158RE.2. These cells express CD8αα dimers, which participate in the thyroid ligand recognition but not in the NK-like activity. The epithelial cell recognition is not restricted by classical MHC class I or class II molecules, although the CD8αα participation in the recognition suggests the involvement of nonclassical MHC molecules. These are the first data to be presented on self-reacting γδ T cells in human epithelium.