Tolerance to the Fetal Allograft. Part A: Is the Fetus an Allograft and is it Object of Immunological Tolerance?

Abstract

In this review, we first discuss the very concept of tolerance and then place it for the fetal allograft in the historical perspective of Sir Peter Medawar citation classic. We then wonder if there is really tolerance in the mainstream immunologist sense, and recall the also classic, but too often forgotten, experiments of Beer and Biillingham We also discuss the limits (in fact recognized in the papers, which is too often neglected) of experiments using weakly immunogenic tumors. Back somehow to Billingham, Head, and Beer notions, we then show that the maternal immune system "senses» the fetal allograft and is active, and that such activation, especially of the innate immune system, is needed for successful pregnancy. The data are then replaced in a modern perspective, and limits of "old" concepts, including my own, are reexamined and challenged.

Keywords: Tolerance, allograft, Medawar, paradigm, systemic, local, split, transient, suppression, regulation, Tcell, Treg, Ts, NK, factors, placenta, decidua.