An immunogenic phenotype in paternal antigen-specific CD8+ T cells at embryo implantation elicits later fetal loss in mice

Immunology and Cell Biology
Lachlan M MoldenhauerSarah A Robertson

Abstract

Central to pregnancy success is a state of T cell tolerance to paternal antigens, which is initiated at conception. The role and regulation of specific phenotypes of CD8+ T cells in mediating pregnancy tolerance is not clear. This study aimed to investigate the impact on pregnancy outcome of altering the cytokine environment during maternal CD8+ T cell priming in early pregnancy. Transgenic Act-mOVA male mice were mated to C57BL/6 (B6) females to generate fetuses expressing ovalbumin (OVA) as a model paternal antigen. OVA-reactive CD8+ OT-I T cells were activated in vitro with OVA in the presence of either transforming growth factor-β1 (TGFB1) plus interleukin-10 (IL10), or IL2, to mimic normal or dysregulated uterine conditions, respectively, and transferred into pregnant mice on gestational day 3.5. OT-I T cells activated with TGFB1 and IL10, like naive OT-I T cells, did not alter embryo implantation or fetal viability. In contrast, OT-I T cells activated with IL2 caused extensive fetal loss manifesting in mid-gestation. IL2-activated OT-I T cells expressed less FOXP3 and higher interferon-γ (IFNG) than cells activated with TGFB1 and IL10. Fetal loss did not occur in females mated with B6 males, demonstrating the antigen spec...Continue Reading

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Citations

Jan 31, 2020·Physiological Reviews·John E Schjenken, Sarah A Robertson
Apr 16, 2019·Frontiers in Immunology·Sarah A RobertsonGustaaf Dekker
Oct 3, 2018·The Journal of Clinical Investigation·Sarah A RobertsonLachlan M Moldenhauer
Jul 11, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne SchumacherAna C Zenclussen
Nov 7, 2020·Molecular Reproduction and Development·Thamiris V MarsicoMateus J Sudano
Jul 18, 2021·Science Immunology·Eva Gillis-BuckTippi C MacKenzie

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