IL-2/JES6-1 antibody complex expands the maternal T regulatory cell pool and alleviates fetal loss in abortion-prone mice.
Date
2024
Authors
Foyle, K.L.
Chin, P.Y.
Merkwirth, C.
Wilson, J.
Hosking, S.L.
Green, E.S.
Chong, M.Y.
Zhang, B.
Moldenhauer, L.M.
Ferguson, G.D.
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Journal article
Citation
American Journal of Pathology, 2024; 194(11):2128-2149
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Abstract
Regulatory T (Treg) cells are essential for immune tolerance of embryo implantation and insufficient Treg cells are implicated in early pregnancy loss. An abortion-prone mouse model was utilized to evaluate the utility of IL-2 complexed with JES6-1 anti-IL-2 antibody (IL-2/JES6-1) to boost uterine Treg cells and improve reproductive success. IL-2/JES6-1 but not IL-2/IgG control administered in the peri-conception phase to CBA/J females mated with DBA/2 males elicited a >2-fold increase in the proportion of CD4+ T cells expressing FOXP3, and an increase in the ratio of FOXP3+ Treg cells to FOXP3- T conventional cells, in the uterus and its draining lymph nodes at embryo implantation that was sustained into mid-gestation. An attenuated phenotype was evident in both thymic-derived and peripheral Treg cells with elevated CTLA4, CD25, and FOXP3 indicating improved suppressive function, as well as increased proliferative marker Ki67. IL-2/JES6-1 treatment reduced fetal loss from 31% to 10%, but this was accompanied by a 6% reduction in late gestation fetal weight, despite comparable placental size and architecture. Similar effects of IL-2/JES6-1 on Treg cells and fetal growth were seen in CBA/J females with healthy pregnancies sired by BALB/c males. These findings show that expanding the uterine Treg cell pool through targeting IL-2 signaling is a strategy worthy of further investigation for mitigating immune-mediated fetal loss.
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Data source: Supplementary data, http://doi.org/10.1016/j.ajpath.2024.07.012
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Copyright 2022 American Society for Investigative Pathology. Published by Elsevier Inc.