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.

Departments of Biomedicine and Nephrology University Hospital Basel and University of Basel 4031 Basel Switzerland

Departments of Biomedicine and Nephrology University Hospital Basel and University of Basel 4031 Basel Switzerland; Institute of Molecular Genetics Czech Academy of Sciences 142 20 Prague Czech Republic

Theodor Kocher Institute University of Bern 3012 Bern Switzerland

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Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2