These data show that T cell-directed expression of the p21 transgene had a dual effect in B6/lpr mice; first, it lessened autoimmune manifestations, due to the transgene effect on IFN-γ production, and second, it limited DN T cell-induced lymphadenopathy by reducing DN T cell hyperactivation and hyperproliferation. Here, CDKN1A is linked to Lymphadenopathy.