Reconsidering the Medawar paradigm placental viviparity existed for eons, even in vertebrates; without a “problem”: Why are Tregs important for preeclampsia in great apes?

Highlights • In opposition to Medawar, placentae exist in invertebrates and above all vertebrates that can reject grafts: see for example the shark “foetal allograft”: no problems. • Placentation exists but does not last long in marsupials: is it because of the threat of a T cell and T cell cytokine attack–also activating NK cells? • Inflammation is needed in implantation but post-implantation must be controlled by Tregs. However, some inflammatory components persist post-implantation in humans. • T cells can be downregulated by complement. • Thus, in human pregnancy continuous controlled inflammation (linked to deep invasion?) exists and alloantigen-specific Treg control may be “borderline” in a first pregnancy. • Model: in great apes, with deep invasion placenta, failure of Treg control or a complement activation (thus Treg downregulation) leads to continuous excess inflammation in PE, more abrupt even in cases of recurrent spontaneous abortion.