Taking advantage of this intriguing anatomical feature, we demonstrated that autoantigen-free microsphere formulations of antisense DNA targeting the primary transcripts of CD40, CD80, and CD86, preferentially accumulated inside PLN, generated Foxp3+ Tregs therein, and in NOD mice, prevented the progression of late-stage dysglycemia to overt clinical diabetes and also achieved reversal of new-onset hyperglycemia and long-term stability of a normoglycemic state (18, 21). The gene discussed is CD40; the disease is diabetes mellitus.