Fetal-cell microchimerism, lymphopoiesis, and autoimmunity

During all human and murine pregnancies, fetal cells enter the maternal circulation and tissues and may persist there for decades. The immune consequences of this phenomenon have been explored for many years as a potential origin of autoimmunity or protection from cancer in women after pregnancy. The leading hypothesis, suggesting that semi-allogenic fetal T cells may trigger a graft-versus-host type of disease, has been supported by several studies showing an increased frequency of fetal-cell microchimerism (FMc) in women affected with systemic sclerosis. However, a large proportion of healthy women or women affected with non-immune disorders also display fetal T cells, challenging the direct pathogenic role of such cells. In addition, recent evidence showing the transfer of various fetal progenitor cells to the mother during gestation has shed new light on the interpretation of microchimerism in autoimmunity. This review discusses the functional capacity of fetal hematopoietic progenitors to form T and B cells in maternal hematopoietic tissues, where they undergo an educational process probably resulting in tolerance to maternal antigens. Therefore, hypotheses other than the transfer of fetal cells to the mother’s circulation should be considered in explaining the observed association of FMc and autoimmune disorders.