Autoimmune gld mutation uncouples suicide and cytokine/proliferation pathways in activated, mature T cells.

Antigen receptor-directed suicide plays an important role in the elimination of potentially autoaggressive immature T cells during thymic differentiation. Here we demonstrated evidence for a second pathway of receptor-directed suicide in mature T cells that is missing in a mutant strain (gld) of mice with an "autoimmune" lymphoproliferative syndrome. The defect is evident within the gld activated T cell and does not require the presence of an antigen-presenting cell for its expression. Receptor-driven suicide is intact in immature T cells of animals with this mutation. These results support the significance of receptor-directed suicide in the mature T cell compartment and suggest that the immune system may use three independent pathways for regulating programmed cell death in shaping and controlling the immune response.