Reproductive outcomes after pregnancy-induced displacement of preexisting microchimeric cells

Science. 2023 Sep 22;381(6664):1324-1330. doi: 10.1126/science.adf9325. Epub 2023 Sep 21.

Abstract

Pregnancy confers partner-specific protection against complications in future pregnancy that parallel persistence of fetal microchimeric cells (FMcs) in mothers after parturition. We show that preexisting FMcs become displaced by new FMcs during pregnancy and that FMc tonic stimulation is essential for expansion of protective fetal-specific forkhead box P3 (FOXP3)-positive regulatory T cells (Treg cells). Maternal microchimeric cells and accumulation of Treg cells with noninherited maternal antigen (NIMA) specificity are similarly overturned in daughters after pregnancy, highlighting a fixed microchimeric cell niche. Whereas NIMA-specific tolerance is functionally erased by pregnancy, partner-specific resiliency against pregnancy complications persists in mothers despite paternity changes in intervening pregnancy. Persistent fetal tolerance reflects FOXP3 expression plasticity, which allows mothers to more durably remember their babies, whereas daughters forget their mothers with new pregnancy-imprinted immunological memories.

MeSH terms

  • Animals
  • Antigens / immunology
  • Cell Plasticity
  • Chimerism*
  • Female
  • Fetus* / cytology
  • Fetus* / immunology
  • Forkhead Transcription Factors / immunology
  • Immune Tolerance*
  • Immunologic Memory*
  • Maternal-Fetal Exchange* / immunology
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy* / immunology
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Antigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse