(A) After activation and expansion of healthy T cells, levels of IL-2 decrease, promoting clonal contraction by apoptosis. Low IL-2 concentration induces the expression of B55β through the binding of CTCF to a motif located within the CpG island of the PPP2R2B promoter. This mechanism promotes the termination of the immune response. (B) In the context of autoimmunity, where T cells are exposed to a proinflammatory environment, PPP2R2B becomes hypermethylated, preventing the binding of CTCF. This impairs the induction of B55β and apoptosis of T cells when IL-2 levels are low. In consequence, survival of self-reactive activated T cells is facilitated and the autoimmune response is perpetuated.