Maternal microchimerism in health and disease

• MMc is commonly present in patients with autoimmune disease healthy individuals, and regulated by regulatory T cells producing transforming growth factor beta (TGF-β), interleukin (IL)-10, and programmed death 1 (PD1).
• The original hypothesis that chimeric T lymphocytes responding to host antigens led to chronic inflammation in a manner similar to graft-versus-host disease (GVHD),the low frequency of cells and the differentiat into hematopoietic and somatic cells.
• Chronic inflammation may occur by host T lymphocyte activation in response to maternal antigens within tissues. Injury or infection may upregulate maternal human leukocyte antigen (HLA) expression, allowing the antigen load to exceed the T cell activation threshold for the otherwise-tolerized host.
• The loss of tolerance to maternal antigens because of hypomorphic immunoregulatory genes may subsequently extend to self-antigens through epitope spreading.

Circulating maternal cells transfer to the fetus during pregnancy, where they may integrate with the fetal immune and organ systems, creating a state of maternal microchimerism (MMc). MMc can persist throughout the child's life, and it has been implicated in the triggering or perpetuation of chronic inflammatory autoimmune diseases, in the context of specific major histocompatibility genes. Correlative data in humans have now been tested in animal model systems. Results suggest that maternal–fetal tolerance may have health implications far beyond the time of pregnancy and into the child's life.