Impact of regulatory T cell therapy on immune cell composition and fetal survival rate in abortion prone mice
F. Idali
A * , H. Golshahi B , L. Katouzian A , F. Notash Haghighat C , S. Rezaii-nia A and M. Jeddi-Tehrani C
+ Author Affiliations
- Author Affiliations
A Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
B Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
C Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
Reproduction, Fertility and Development 35(9) 504-517 https://doi.org/10.1071/RD22267
Published online: 22 May 2023
© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing
Abstract
Context: Implantation of fertilised eggs and survival of a semi-allogenic embryo rely on the interactions between the cells and molecules preparing the uterus. We investigated the effect of regulatory T cell (Treg) therapy on the mechanism of local immune tolerance of mice prone to spontaneous abortion.
Methods: Naive T cells were stimulated in vitro with 17β-oestradiol (E2), progesterone (P4) and TGF-β1 for 96 h to generate induced Tregs (iTreg). The iTregs were injected into DBA/2-mated pregnant CBA/J female mice (abortion prone model). On day 14 of pregnancy, mice were killed and decidual and placental tissues were collected for cellular composition analysis.
Results: Abortion prone mice (PBS treated) showed significantly lower survival rates (P < 0.0001), increased CD3+CD8+ (P < 0.05), lower IDO+ (P < 0.05) and increased natural killer cells (uNK) cell numbers (P < 0.001) in the uterus, as well increased NK cells in the placenta (P < 0.05) than in normal pregnant mice (CBA/J × BALB/c). Adoptive transfer of iTregs increased fetal survival in abortion-prone mice (P < 0.01) and histopathological evaluation revealed a significantly decreased number of uNK cells in the uterus of TGF-β1-, E2- and P4-iTregs (P < 0.05, P < 0.0001 and P < 0.05, respectively) than in the PBS treated group. In the placenta, we found significantly lower numbers of uNK cells from TGF-β1-, E2- and P4-iTregs than in the PBS treated group (P < 0.05, P < 0.05 and P < 0.01, respectively).
Conclusions: We propose that modulation of uterine NK cell activity through immunotherapy using Treg cells should be given more attention as an immunological strategy in the treatment of recurrent miscarriage.
Keywords: abortion, CD8+ T cells, indoleamine 2,3-dioxygenase, macrophages, natural killer cells, oestrogen, progesterone, regulatory T cells, transforming growth factor.
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