Naturally arising regulatory T (TR) cells, represented by CD25+CD4+ TR cells, play an essential role in maintaining immunological self-tolerance. This T cell-mediated dominant control of the immune response not only inhibits the development of autoimmune disease, but also impedes effective immunosurveillance against autologous tumor cells. Attenuation of TR cell-mediated immune suppression can therefore evoke effective tumor immunity in otherwise nonresponsive animals. This common regulatory mechanism for autoimmunity and tumor immunity can be exploited when devising a novel immunotherapy for cancer.