Th2 alloimmunity counteracts Th17-type response in the neonatal establishment of lymphoid chimerism.

The neonatal period of life is described as particularly susceptible to develop tolerance. This status of neonatal tolerance has been studied for decades since the discovery that semiallogeneic spleen cells inoculated at birth can induce donor-type graft acceptance. The host neonatal T‑cell compartment that may account for this propensity to develop tolerance is mostly characterized by a Th2-type polarized response and a default in the cytotoxic T lymphocyte (CTL) functions that allow the establishment of lymphoid chimerism and promote donor-type graft survival. We highlighted a new role of alloreactive Th17 cells as a critical barrier to neonatal tolerance that prevents this lymphoid chimerism and further demonstrated that the Th2 immune deviation is essential to control this Th17-type response. We discuss here the potential impact of breaking the tolerizing effects of exposure of the developing offspring to alloantigens in the induction of Th17-type immunity.