Binding of Peripheral Blood and Thyroidal T Lymphocytes to Thyroid Cell Monolayers: Possible Role of “Homing-Like” Receptors in the Pathogenesis of Thyroid Autoimmunity

The specific binding of blood lymphocyte populations to non-antigenic receptors on high endothelial cells in peripheral lymphoid organs is well established. Such “homing” receptors in target tissues may also play a role in the early phase of organ specific autoimmunity. In this study binding of peripheral blood and thyroid-derived T cells to human thyroid (THY) cells was examined. Binding was measured as the percentage 51Cr-labelled T cells bound to THY monolayers. Interferon-γ(IFN-γ) enhanced the binding of peripheral blood T cells (PBL-T) from patients with Graves' disease (GD) and normals, but not from patients with Hashimoto's thyroiditis (HT), to allogeneic THY monolayers. The binding of T cells from patients with HT to untreated allogeneic THY monolayers was significantly greater than that for T cells from patients with GD or normals. TSH inhibited the IFN-/enhancement of binding of PBL-T from 4 normals and one HT patient to both allogeneic (n=5) and autologous (n=4) THY monolayers. Intra-thyroid T cells (ITL-T) bound to autologous THY monolayers significantly more than PBL-T from the same patient, while ITL from patients with HT or Graves' disease bound more than their PBL-T to both allogeneic and autologous THY monolayers. ITL-T, but not PBL-T, bound significantly more to autologous THY than to autologous thyroid-derived fibroblast monolayers. When a THY monolayer, treated with IFN-γ, was preincubated with a monoclonal anti-DR antibody T cell binding was not inhibited suggesting that cell surface Class II HLA (DR) antigen did not play a major role in the IFN-γ stimulated binding. Cell fractionation experiments indicated that the T lymphocyte subpopulations from patients with GD which bound to THY monolayers comprised, mainly, helper/inducer T cells. Since the number of thyroid-derived T cells binding to autologous thyroid-cells is much greater than can be accounted for by antigen recognition the existence of tissue specific “homing-like” receptors on thyroid cells, and the corresponding molecule on T lymphocytes, is suggested. Binding of T cells to such “homing-like” receptors could explain the initial influx of immunocompetent cells into target tissues which may be a prerequisite for the specific interaction of autoantibodies and sensitized T cells with cell surface antigens.