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Adoptive Cell Therapy With Induced Regulatory T Cells Normalises the Abortion Rate in Abortion-Prone Mice Publisher Pubmed



Idali F1 ; Rezaiinia S1 ; Golshahi H2 ; Fatemi R1 ; Naderi MM3 ; Goli LB1 ; Zarnani AH1, 4 ; Jedditehrani M5
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Authors Affiliations
  1. 1. Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Evin, Tehran, Iran
  2. 2. Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Evin, Tehran, Iran
  3. 3. Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Evin, Tehran, Iran
  4. 4. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Enghelab Ave, Tehran, Iran
  5. 5. Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

Source: Reproduction# Fertility and Development Published:2021


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. © 2021 CSIRO.
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