Fetal–maternal microchimerism: impact on hematopoietic stem cell transplantation

Reciprocal cell traffic between mother and fetus during pregnancy gives rise to postpartum fetal–maternal lymphohematopoietic microchimerism, which is frequently detected in blood or tissue from healthy individuals. Although such microchimerism has been implicated in the pathogenesis of autoimmune diseases and tissue repair, recent clinical experiences have suggested the association of microchimerism with acquired immunologic hyporesponsiveness to non-inherited maternal HLA antigens (NIMAs) or inherited paternal HLA antigens (IPAs); T cell-replete HLA-haploidentical hematopoietic stem cell transplantation from a microchimeric IPA/NIMA-mismatched donor confers relatively lower incidence of severe graft-versus-host disease. The underlying mechanisms by which fetal–maternal microchimerism contributes to IPA/NIMA-specific tolerance are still elusive, although emerging experimental evidence suggests an involvement of the central deletion of IPA/NIMA-reactive T cells, the induction of peripheral regulatory T cells, and affinity-dependent modulation of NIMA-reactive B cells.