Innate immune signals foster adaptive immunity through activation of antigen‐presenting cells. Recent in vitro evidence suggests that innate signaling may also contribute to immunity by countering the effects of regulatory T cells (T‐regs), counter‐regulation. We present in vivo evidence using a transgenic skin allograft model that the function of T‐regs is lost in the setting of acute skin transplantation but remains intact when grafts were transplanted 1 month prior to allow surgery‐induced inflammation to abate. Our findings identify T‐reg counter‐regulation as a naturally occurring process that accompanies transplantation and an important barrier to T‐reg–mediated tolerance. Our finding further highlights the central role of regulatory cell deactivation in the initiation of the immune response.