Is the immune system necessary for placental reproduction? A hypothesis on the mechanisms of alloimmunotherapy in recurrent spontaneous abortion.

Recurrent spontaneous abortion is being treated with alloimmunotherapy which consists of the inoculation of allogeneic mononuclear cells. However the mechanisms explaining the benefits of this therapy are not clear yet. Taking the immunotrophic hypothesis as the paradigm of the field of reproductive immunology, hereby we present a hypothesis to propose a role for the immune system in reproduction and at the same time to explain how alloimmunotherapy may work. We base our view on several facts: first, immunodeficient mice reproduce--albeit their progeny may not be as robust and numerous as that from normal individuals. Second, maternal lymphocytes cross the placenta and may induce graft versus host disease. Third, graft versus host disease in newborn F1 mice inoculated with paternal lymphocytes can be prevented by inoculation of the mother with the same paternal lymphocytes before and during pregnancy. We propose that: 1) the immune system by itself is not necessary for placental reproduction; 2) the immune system plays its major role in reproduction by counteracting the allogeneic response generated against the fetus; 3) recurrent spontaneous abortion represents a type of graft versus host disease induced by maternal cells infiltrating the fetus; and 4) alloimmunotherapy induces an antiidiotypic response necessary to counteract the graft versus host reaction in the fetus.