ArticleThe Journal of clinical investigation2021
Pregnancy-induced humoral sensitization overrides T cell tolerance to fetus-matched allografts in mice.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Reversing pregnancy-induced B cell sensitization to facilitate the induction of transplant tolerance in postpartum recipients.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- MX1Journal of translational medicine · 2026Article
- Pregnancy-shaped donor-directed alloimmune recall in husband-to-wife kidney transplantation: an integrative mechanistic framework.Frontiers in immunology · 2026Review
- Evidence for Maternal Autoantibodies in the Pathogenesis of Preterm Birth.medRxiv : the preprint server for health sciences · 2025Article
- Resolving ScRNA-Seq Signatures of Antigen-Specific CD4bioRxiv : the preprint server for biology · 2025Article
- Cell-intrinsic CD4 T cell tolerance: a new frontier in therapy?Trends in immunology · 2025Review
- Fetoplacental extracellular vesicles deliver conceptus-derived antigens to maternal secondary lymphoid tissues for immune recognition.JCI insight · 2025Article
- CAR Treg synergy with anti-CD154 promotes infectious tolerance and dictates allogeneic heart transplant acceptance.JCI insight · 2025Article
- Hyporesponsive fetus-specific T cell responses in multiparous human pregnancy.Frontiers in immunology · 2025Article
- B Cell Responses to the Placenta and Fetus.Annual review of pathology · 2025Review
- Clinical relevance of feto-maternal microchimerism in (hematopoietic stem cell) transplantation.Seminars in immunopathology · 2024Review
- First Longitudinal Analysis of the Immunological Mechanism at Play in Uterus Transplantation.Transplantation direct · 2024Article
- Pregnancy dedifferentiates memory CD8+ T cells into hypofunctional cells with exhaustion-enriched programs.JCI insight · 2024Article
- A case for the study of native extracellular vesicles.Frontiers in oncology · 2024Article
- Sex as a biological variable: Mechanistic insights and clinical relevance in solid organ transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Review
- Regulatory T cell adoptive transfer alters uterine immune populations, increasing a novel MHC-IIFrontiers in immunology · 2023Article
- Extracellular vesicles and immune response during pregnancy: A balancing act.Immunological reviews · 2022Review
- Trophoblast antigens, fetal blood cell antigens, and the paradox of fetomaternal tolerance.The Journal of experimental medicine · 2022Article
- Toward an understanding of allogeneic conflict in pregnancy and transplantation.The Journal of experimental medicine · 2022Review
- The impact of preformed donor-specific antibodies in living donor liver transplantation according to graft volume.Immunity, inflammation and disease · 2022Article
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11 authors at 2 institutions in 1 country.
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Abstract
Immunological tolerance to semiallogeneic fetuses is necessary to achieving successful first pregnancy and permitting subsequent pregnancies with the same father. Paradoxically, pregnancy is an important cause of sensitization, resulting in the accelerated rejection of offspring-matched allografts. The underlying basis for divergent outcomes following reencounter of the same alloantigens on transplanted organs versus fetuses in postpartum females is incompletely understood. Using a mouse model that allows concurrent tracking of endogenous fetus-specific T and B cell responses in a single recipient, we show that semiallogeneic pregnancies simultaneously induce fetus-specific T cell tolerance and humoral sensitization. Pregnancy-induced antibodies, but not B cells, impeded transplantation tolerance elicited by costimulation blockade to offspring-matched cardiac grafts. Remarkably, in B cell-deficient mice, allogeneic pregnancy enabled the spontaneous acceptance of fetus-matched allografts. The presence of pregnancy-sensitized B cells that cannot secrete antibodies at the time of heart transplantation was sufficient to precipitate rejection and override pregnancy-established T cell tolerance. Thus, while induction of memory B cells and alloantibodies by pregnancies establishes formidable barriers to transplant success for multigravid women, our observations raise the possibility that humoral desensitization will not only improve transplantation outcomes, but also reveal an unexpected propensity of multiparous recipients to achieve tolerance to offspring-matched allografts.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.