Adoptive cell therapy with induced regulatory T cells normalises the abortion rate in abortion-prone mice
F. Idali A F * , S. Rezaii-nia A * , H. Golshahi B , R. Fatemi A , M. M. Naderi C , L. Ballaii Goli A , A. H. Zarnani A D and M. Jeddi-Tehrani E
+ Author Affiliations
- Author Affiliations
A Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Evin, Tehran, Iran.
B Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Evin, Tehran, Iran.
C Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Evin, Tehran, Iran.
D Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Enghelab Ave, Tehran, Iran.
E Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
F Corresponding author. Email: f.ideali@ari.ir; farahid@yahoo.com
Reproduction, Fertility and Development - https://doi.org/10.1071/RD20063
Submitted: 3 March 2020 Accepted: 13 November 2020 Published online: 15 December 2020
Abstract
Ovarian hormones drive in vivo generation of regulatory T cells (Tregs) during pregnancy. Little is known about the therapeutic potential of in vitro hormone-derived Tregs in pregnancy loss. We investigated the effects of hormone-induced Tregs in a murine model of abortion. CD4+CD25– T cells were isolated from the spleens of CBA/J mice and stimulated with either 17β-oestradiol (E2), progesterone (P4) or transforming growth factor-β1 (TGFB1) plus retinoic acid (RA) for 4 days to generate induced Tregs (iTregs). On Days 1–4 of gestation, DBA/2-mated pregnant CBA/J female mice (abortion prone) were injected intravenously with iTregs or Tregs isolated from normal BALB/c-mated pregnant CBA/J mice (np-Tregs). On Day 14, the number of resorbed fetuses was assessed. Serum interferon (IFN)-γ and uterine forkhead box p3 (Foxp3) expression was analysed by ELISA and immunohistochemistry respectively. Using a 3H-thymidine incorporation assay, isolated CD4+CD25+ Tregs induced by the different treatments suppressed the proliferation of CD4+CD25– T cells. Adoptive transfer of iTregs (from all induction groups) significantly decreased fetal resorption in abortion-prone mice. There were no significant changes in serum IFN-γ concentrations after the adoptive transfer of iTregs or np-Tregs. Immunohistochemistry revealed significantly higher Foxp3 expression in gravid uteri from mice injected with np-Tregs and P4-induced iTregs than in the phosphate-buffered saline-treated group. The findings of this study indicate a potential therapeutic benefit of in vitro-induced Tregs in patients with recurrent abortion.
Keywords: abortion, induced regulatory T cells, 17β-oestradiol, progesterone, transforming growth factor β1.
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