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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 505-515 |
| Number of pages | 11 |
| Journal | Cell |
| Volume | 162 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 1 2015 |
Funding
We thank Dr. Marc Jenkins for providing 2W1S-OVA transgenic mice and Drs. James Moon, Louis Muglia, Joseph Qualls, Anne Stevens, Kevin Urdahl for helpful discussions. This work as supported by the NIH-NIAID through awards R01-AI100934 and R21-AI112186 (to S.S.W.) and the NIH-NHLBI through award R01-HL103745 (to A.F.S.). S.S.W. holds an Investigator in the Pathogenesis of Infectious Disease award from the Burroughs Wellcome Fund.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology