Review

Immunological implications of pregnancy-induced microchimerism

  • Nature Reviews Immunology 17, 483494 (2017)
  • doi:10.1038/nri.2017.38
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Abstract

Immunological identity is traditionally defined by genetically encoded antigens, with equal maternal and paternal contributions as a result of Mendelian inheritance. However, vertically transferred maternal cells also persist in individuals at very low levels throughout postnatal development. Reciprocally, mothers are seeded during pregnancy with genetically foreign fetal cells that persist long after parturition. Recent findings suggest that these microchimeric cells expressing non-inherited, familially relevant antigenic traits are not accidental 'souvenirs' of pregnancy, but are purposefully retained within mothers and their offspring to promote genetic fitness by improving the outcome of future pregnancies. In this Review, we discuss the immunological implications, benefits and potential consequences of individuals being constitutively chimeric with a biologically active 'microchiome' of genetically foreign cells.

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Acknowledgements

The writing of this Review and reference to the authors' own work were made possible through funding by Cusanuswerk-Studienförderung (to I.A.S.); Deutsche Forschungsgemeinschaft (AR232/25-1 in KFO296 and AR232/27-1 to P.C.A.); the US National Institutes of Health, Office of the Director (DP1AI131080 to S.S.W.); the US National Institute of Allergy and Infectious Disease (R01AI100934 and R01AI120202 to S.S.W.); and the March of Dimes Foundation (FY15-254 to S.S.W.). S.S.W. is a Burroughs Wellcome Fund Investigator in the pathogenesis of infectious disease and is a Howard Hughes Medical Institute Faculty Scholar.

Author information

Affiliations

  1. Division of Infectious Disease, Cincinnati Children's Hospital.

    • Jeremy M. Kinder
    •  & Sing Sing Way
  2. Perinatal Institute, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.

    • Jeremy M. Kinder
    •  & Sing Sing Way
  3. Laboratory for Experimental Feto-Maternal Medicine, Department of Obstetrics and Prenatal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

    • Ina A. Stelzer
    •  & Petra C. Arck

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Sing Sing Way.

Supplementary information

Word documents

  1. 1.

    Supplementary information S1 (table)

    Cellular phenotype of maternal and fetal microchimeric cells during pregnancy and after parturition

Glossary

Immunological identity

The signature of distinct protein antigens that is encoded by the unique DNA of each individual, which includes MHC haplotype alleles and other alloantigens.

Viviparity

Development of offspring inside the body of the parent that results in the birth of live offspring capable of independent existence.

Fetal tolerance

The processes that allow fetal cells and tissues that express genetically foreign paternal antigens to avoid immune rejection and coexist in harmony inside expecting mothers during pregnancy.

Microchimeric cells

Rare cells found in one individual that originate from another individual and are genetically distinct from the host individual.

Non-inherited maternal antigens

(NIMAs). The half of genetically encoded maternal antigens that are not transmitted to an offspring by classical Mendelian inheritance.

Allogeneic pregnancies

Pregnancies that occur as the result of mating between individuals that are genetically distinct. For genetically identical, inbred animal strains, this refers to matings between unique male and female strains that have discordant MHC haplotypes, a setting that recapitulates the natural diversity of MHC alleles among individuals in outbred populations.

Peripherally induced Treg cells

CD4+ T cells that are induced to express forkhead box protein P3 and acquire immunosuppressive properties by cognate antigen stimulation in extrathymic peripheral tissues.

Maternal–fetal histocompatibility

The degree of similarity between genetically encoded MHC alleles in each mother–child pair.