A minimum number of autoimmune T cells to induce autoimmunity?

•Determination of minimal T cell number for autoimmunity in a mouse model.•2–5 autoimmune T cells can induce lethal diabetes.•Outgrowth of dominant T cell clonotype during disease induction.•Results support quorum sensing and stochastic expansion of dominant clonotypes. While autoimmune T cells are present in most individuals, only a minority of the population suffers from an autoimmune disease. To better appreciate the limits of T cell tolerance, we carried out experiments to determine how many autoimmune T cells are required to initiate an experimental autoimmune disease. Variable numbers of autoimmune OT-I T cells were transferred into RIP-OVA mice, which were injected with antigen-loaded DCs in a single footpad; this restricted T cell priming to a few OT-I T cells that are present in the draining popliteal lymph node. Using selective plane illumination microscopy (SPIM) we counted the number of OT-I T cells present in the popliteal lymph node at the time of priming. Analysis of our data suggests that a single autoimmune T cell cannot induce an experimental autoimmune disease, but a “quorum” of 2–5 autoimmune T cells clearly has this capacity.