The markers of increased inflammation included multi-organ lymphocyte infiltration with splenomegaly and lymphadenopathy, a progressive increase in autoantibodies production that was variable with respect to the exact autoreactivity detected, and a progressive increase in the numbers of T cells with an activated phenotype comparing DKO-moderate and DKO-severe Foxp3-Cre Tet2/3fl/fl mice (Fig. 1I, J, Fig. 5, Suppl. This evidence concerns the gene FOXP3 and Splenomegaly.