Graft-Matched Pregnancy Imparts Profound Epigenetic Changes onto Alloreactive Memory T Cells to Enforce a Phenotypic and Transcriptional State of Tolerance
| العنوان: | Graft-Matched Pregnancy Imparts Profound Epigenetic Changes onto Alloreactive Memory T Cells to Enforce a Phenotypic and Transcriptional State of Tolerance |
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| المؤلفون: | Jared Pollard, Dengping Yin, Malay Mandal, Fotini Gounari, Maria-Luisa Alegre, Anita Chong |
| المصدر: | The Journal of Immunology. 208:175.28-175.28 |
| بيانات النشر: | The American Association of Immunologists, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | Pregnancy is an immunological paradox, where the maternal immune system develops tolerance to a semi-allogeneic fetus, yet pregnancy is a major sensitizing event in clinical transplantation. We previously reported that pregnancy robustly tolerizes fetus-specific T cells, allowing for the spontaneous acceptance of fetus-matched allografts when B cells and alloantibodies are absent at the time of transplantation(1). In this study, we report that mice sensitized to 2WOVA.B/c allogeneic skin grafts (Memory) underwent successful pregnancies comparable to Naïve mice when mated with 2WOVA.B/c males. We utilized a high-dimensional multi-omics approach to characterize post-partum (PP) fetus-specific T cells from Naïve or Memory mice after semi-allogeneic pregnancies. Strikingly, pregnancy induced fetus-specific naïve and memory T cells to achieve a nearly identical phenotype, characterized by upregulation of co-inhibitory molecules FR4, CD73, PD1, and CTLA4 in CD4+FoxP3- Tconvs and upregulated PD-1, FR4 and Lag3 in CD8+ T cells. We confirmed that naïve and memory PP CD8+ T cells acquired similar transcriptional profiles via RNA-Seq; unexpectedly, pregnancy induced profound epigenetic modifications in memory, but not naïve, CD8+ T cells. In vitro studies indicated reduced TNF aproduction by memory PP CD4+ and CD8+ T cells, and experiments examining their response to fetus-matched allografts are ongoing. Our studies suggest that significant epigenetic imprinting is necessary to constrain memory T cells to preserve fetal viability during semi-allogeneic pregnancy. These findings may provide insights into controlling antigen-specific memory T cells, a major barrier to clinical transplant success |
| تدمد: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.208.supp.175.28 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::98ccd76468345cd52d2fb3ab3bb66d27 https://doi.org/10.4049/jimmunol.208.supp.175.28 |
| رقم الانضمام: | edsair.doi...........98ccd76468345cd52d2fb3ab3bb66d27 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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| DOI: | 10.4049/jimmunol.208.supp.175.28 |