Adoptive cell therapy with induced regulatory T cells normalises the abortion rate in abortion-prone mice.

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. Recurrent spontaneous abortion (RSA) has been associated with a deficiency in maternal regulatory T cells (Tregs). Adoptive transfer of Tregs may play a role in protecting embryos in women with RSA. Adoptive transfer of induced (i) Tregs resulted in normal pregnancy rates in abortion-prone mice. iTregs may have potential therapeutic benefits in patients with RSA. [ABSTRACT FROM AUTHOR]