This is supported by three main lines of evidence: first, the demonstration that Tfr cells preferentially derive from thymic Foxp3+ Tregs, with a self-biased T cell receptor (TCR) repertoire [11–13, 22–26]; secondly, the observation that a specific Tfr deletion in mouse models leads to the emergence of self-reactive antibodies and autoimmunity [23, 27–30]; finally, the growing number of human studies finding correlations between the manifestation of autoimmune diseases and quantitative or qualitative alterations in blood Tfr cells of autoimmune patients [31, 32]. This evidence concerns the gene TFRC and autoimmune disease.