Do maternal cells trigger or perpetuate autoimmune diseases in children?

In human pregnancy, cell traffic during pregnancy is bi-directional, with maternal cells passing into the fetal circulation and fetal into the maternal. Maternal cells can engraft in infants with severe combined immunodeficiency (SCID), unbothered by a defensive host immune system [1-7]. In a large cohort of infants with SCID, MMc was detected in 40%, and graft-versus-host disease (GVHD) developed in 76% [7]. Both maternal T and B lymphocytes have been described engrafting into immunodeficient infants [1,3-7], but unlike stem cell transplantation, when donor cells functionally replace the host immune system, maternal cells physically replace but do not function for the child's immune system. The functional capacity of chimeric maternal cells is not well-defined. In vitro, chimeric maternal cells respond poorly to specific mitogens such as antigen or allogenic stimulator cells [1,5,6]. Chimeric maternal T cells do respond to non-specific mitogens such as IL-2, anti-CD3 antibodies or PHA, and maternal cell lines have been grown from the blood of immunodeficiency patients. These maternal cell lines were able to proliferate normally and express maternal HLA molecules [4-7]. Although T lymphocyte activation markers have been detected on chimeric maternal lymphocytes and MMc has been associated with GVHD, 40% of patients with detectable MMc never developed GVHD, suggesting that regulatory mechanisms control the engrafted maternal lymphocytes. One reason for the limited ability of maternal T lymphocytes to respond to specific antigens may be the limited T cell receptor repertoire in engrafted maternal cells [6]. Thus, a limited number of maternal T lymphocyte clones may be transported into the fetus and expand in response to non-specific stimuli. On the other hand, a random selection of maternal cells may travel to the fetus and specific clones expand by an antigenic stimulus yet to be identified, leading to clonal over-representation in the total population. The rate of p