title: Fetal intervention increases maternal T cell awareness of the foreign conceptus and can lead to immune-mediated fetal demise.
abstract: Fetal interventions to diagnose and treat congenital anomalies are growing in popularity but often lead to preterm labor. The possible contribution of the maternal adaptive immune system to postsurgical pregnancy complications has not been explored. We recently showed that fetal intervention in mice increases maternal T cell trafficking into the fetus and hypothesized that this process also may lead to increased maternal T cell recognition of the foreign conceptus and subsequent breakdown in maternal-fetal tolerance. In this study, we show that fetal intervention in mice results in accumulation of maternal T cells in the uterus and that these activated cells can produce effector cytokines. In adoptive transfer experiments, maternal T cells specific for a fetal alloantigen proliferate after fetal intervention, escape apoptosis, and become enriched compared with endogenous T cells in the uterus and uterine-draining lymph nodes. Finally, we demonstrate that such activation and accumulation can have a functional consequence: in utero transplantation of hematopoietic cells carrying the fetal alloantigen leads to enhanced demise of semiallogeneic fetuses within a litter. We further show that maternal T cells are necessary for this phenomenon. These results suggest that fetal intervention enhances maternal T cell recognition of the fetus and that T cell activation may be a culprit in postsurgical pregnancy complications. Our results have clinical implications for understanding and preventing complications associated with fetal surgery such as preterm labor.
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Marta
authors.initials: M
authors.lastname: Wegorzewska
authors.forename: Amar
authors.initials: A
authors.lastname: Nijagal
authors.forename: Charissa M
authors.initials: CM
authors.lastname: Wong
authors.forename: Tom
authors.initials: T
authors.lastname: Le
authors.forename: Ninnia
authors.initials: N
authors.lastname: Lescano
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Tang
authors.forename: Tippi C
authors.initials: TC
authors.lastname: MacKenzie
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D005260:Female; D046128:Fetal Therapies; D005333:Fetus / Q000276:immunology; D054502:Histocompatibility, Maternal-Fetal / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation*; D014599:Uterus / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit