Feto-maternal allo-immunity, regulatory T cells and predisposition to auto-immunity. Does it all start in utero?

During gestation, maternal cells traffic to the fetus leading to the natural phenomenon of microchimerism. Although their persistence in offspring has been associated with several autoimmune disorders, the precise role of maternal cells in these disorders remains unclear. We aimed to evaluate whether alloreactive maternal T cells could directly trigger a graft-vs.-host like reaction or indirectly influence the development of the offspring's regulatory T cells (Treg) favoring autoimmunity. In a specific breeding strategy, we recently reported that maternal allogeneic T cells changed fetal Treg development and their quantities in mesenteric lymph nodes, leading to early signs of inflammation in the gut later in life. Although maternal microchimeric T cells were found in newborn tissues, we could not detect any cells in the gut from adult offspring where the inflammation occurred. Thus, strongly alloreactive maternal microchimeric T cells may indirectly drive the offspring to gut inflammation. We believe these results suggest a new mechanism for predisposition to auto-immunity.