Adoptive cell therapy with induced regulatory T cells normalises the abortion rate in abortion-prone mice
| Autor: | Mahmood Jeddi-Tehrani, Mohammad Mehdi Naderi, Farah Idali, S Rezaii-Nia, L Ballaii Goli, H Golshahi, Ramina Fatemi, Amir-Hassan Zarnani |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Adoptive cell transfer chemical and pharmacologic phenomena Gestational Age Reproductive technology Biology Lymphocyte Activation T-Lymphocytes Regulatory Andrology Cell therapy Transforming Growth Factor beta1 Interferon-gamma Endocrinology Interferon Pregnancy Genetics medicine Animals IL-2 receptor Molecular Biology reproductive and urinary physiology Cells Cultured Progesterone Cell Proliferation Fetus Estradiol Uterus FOXP3 hemic and immune systems Forkhead Transcription Factors Fetal Resorption Adoptive Transfer Coculture Techniques Abortion Spontaneous Disease Models Animal Reproductive Medicine Mice Inbred DBA Mice Inbred CBA Animal Science and Zoology Female Developmental Biology Biotechnology Hormone medicine.drug |
| Zdroj: | Reproduction, fertility, and development. 33(3) |
| ISSN: | 1031-3613 |
| Popis: | Ovarian hormones drive invivo generation of regulatory T cells (Tregs) during pregnancy. Little is known about the therapeutic potential of invitro 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 invitro-induced Tregs in patients with recurrent abortion. |
| Databáze: | OpenAIRE |
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