Proliferation of T8-positive cytolytic T lymphocytes in response to thyroglobulin in human autoimmune thyroiditis: Analysis of cell interactions and culture requirements

These experiments were designed to analyze the involvement of T-lymphocyte subpopulations in autoimmune thyroid disorders such as Graves' Disease (GD) and Hashimotos' Disease (HD). In a first set of experiments, lymphocytes isolated from thyroid infiltrates or from peripheral blood of GD and HD patients were analyzed for the expression of various surface antigens. While HLA-DR+ T cells were numerous among thyroid infiltrating T lymphocytes in both groups of patients, the proportions of T8+ cells (as defined by their reactivity with the B 9.4 monoclonal antibody specific for T8 surface molecule) were strikingly different in HD and GD. In the latter group of patients only 19% of infiltrating T cells were T8+, whereas these cells represented approximately 50% in four HD patients. Given the previous demonstration that all T cells expressing T8 antigen are cytolytic T lymphocytes (CTL) or their precursors (CTL-P) in conjunction with the fact that lymphocytes from HD or GD patients are known to proliferate in vitro in response to human tg (Htg), we further analyzed the T-cell subset(s) responsible for in vitro proliferation to Htg. In these experiments, peripheral blood T lymphocytes purified from patients with GD or HD were cultured with 1 μg/ml Htg and irradiated autologous T-depleted mononuclear cells as the source of antigen presenting cells (APC). The proportions of T8+ cells declined considerably during culture in GD patients, but at Days 6 to 9, T8+ cells represented as much as 51% of cultured T lymphocytes from patients with HD. Moreover, the majority of T8+ cells were medium-large size lymphoblasts. Removal of Htg at Day 6 resulted in both abrogation of proliferative responsiveness and in decreases of T8+ percentages. Further analysis of the cell interactions leading to T8+ cell proliferation in response to Htg showed that helper/inducer T cells, as defined by 5 9 antigen expression, were strictly required. Collectively, these features are reminiscent of the T-cell involvement in experimental autoimmune thyroiditis of mice and stress for the first time the potential role of CTL in tissue damage occurring in Hashimoto's thyroiditis.