CD4 and Autoimmunity: To ask the question of whether CD4 regulation and memory could have co-evolved in the common placental ancestor we reasoned that mice deficient in FoxP3 (no Tregs) and also deficient in OX40 and CD30 (no high affinity antibodies and memory) would mimic at least to some extent the immune system of the common mammalian ancestral immune system seen in monotremes, and would not exhibit autoimmunity.