title: Cross-Generational Reproductive Fitness Enforced by Microchimeric Maternal Cells.
abstract: Exposure to maternal tissue during in utero development imprints tolerance to immunologically foreign non-inherited maternal antigens (NIMA) that persists into adulthood. The biological advantage of this tolerance, conserved across mammalian species, remains unclear. Here, we show maternal cells that establish microchimerism in female offspring during development promote systemic accumulation of immune suppressive regulatory T cells (Tregs) with NIMA specificity. NIMA-specific Tregs expand during pregnancies sired by males expressing alloantigens with overlapping NIMA specificity, thereby averting fetal wastage triggered by prenatal infection and non-infectious disruptions of fetal tolerance. Therefore, exposure to NIMA selectively enhances reproductive success in second-generation females carrying embryos with overlapping paternally inherited antigens. These findings demonstrate that genetic fitness, canonically thought to be restricted to Mendelian inheritance, is enhanced in female placental mammals through vertically transferred maternal cells that promote conservation of NIMA and enforce cross-generational reproductive benefits.
authors.affiliation: Division of Infectious Diseases and Perinatal Institute, Cincinnati Children's Hospital. 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Kinder
authors.affiliation: Division of Infectious Diseases and Perinatal Institute, Cincinnati Children's Hospital. 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Tony T
authors.initials: TT
authors.lastname: Jiang
authors.affiliation: Division of Infectious Diseases and Perinatal Institute, Cincinnati Children's Hospital. 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Ertelt
authors.affiliation: Division of Infectious Diseases and Perinatal Institute, Cincinnati Children's Hospital. 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xin
authors.affiliation: Center for Fetal Cellular and Molecular Therapy, Cincinnati Children's Hospital. 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Strong
authors.affiliation: Center for Fetal Cellular and Molecular Therapy, Cincinnati Children's Hospital. 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Aimen F
authors.initials: AF
authors.lastname: Shaaban
authors.affiliation: Division of Infectious Diseases and Perinatal Institute, Cincinnati Children's Hospital. 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Electronic address: singsing.way@cchmc.org.
authors.forename: Sing Sing
authors.initials: SS
authors.lastname: Way
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D046528:Chimerism; D005260:Female; D005333:Fetus / Q000276:immunology*; D056084:Genetic Fitness; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D008322:Mammals / Q000276:immunology / Q000502:physiology*; D051379:Mice; D010920:Placenta / Q000276:immunology; D011247:Pregnancy / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000941:Antigens