Long-term feto-maternal microchimerism revisited: Microchimerism and tolerance in hematopoietic stem cell transplantation.

Bidirectional fetal-maternal cell traffic during pregnancy gives rise to stable persistence of minute amounts of allogeneic cells both in the mother and in her offspring, a phenomenon called long-term fetal or maternal microchimerism. Over the past decade, increasing attention has been devoted to elucidating the biological relevance of such reciprocal microchimerism, unveiling its conflicting roles in either immune sensitization or tolerance induction against fetal or maternal alloantigens. Recent studies in mice and humans have highlighted the significance of fetal-maternal microchimerism in the induction and maintenance of CD4(+)CD25(+) and CD8(+) T regulatory cells that counterbalance the immune responses to fetal or maternal antigens mediated by T effector cells. Consistent with these observations, T-cell-replete hematopoietic stem cell transplantation between mutually microchimeric mothers and their HLA-haploidentical offspring has been shown to be feasible, although the degree of microchimerism-associated tolerance appears to substantially differ among the cases. Since in vitro or trans-vivo assays to detect antigen-specific tolerance in the context of the T regulator versus T effector balance are now available, future clinical studies incorporating these tests into the criteria for donor selection are warranted to more precisely define the relevance of fetal-maternal microchimerism in allotolerance and immune homeostasis after hematopoietic stem cell transplantation.