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Decreased Frequency of CD8+HLA-G+ T Cell in the Peripheral Blood of Primary Unexplained Infertile Females

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Abstract

Most of the findings have focused on the importance of CD4+HLA-G+ and CD8+HLA-G+ regulatory T cells (Treg) during pregnancy. It has been demonstrated that these HLA-G+ T cell subsets could induce maternal immune tolerance against semi-allogenic conceptus during pregnancy. There are only a few experiments regarding the Treg cells in the context of unexplained infertility (UI). Thirty-five participants including 18 primary unexplained infertile and 17 fertile females were enrolled in this study. A total of 3–5 ml blood samples were taken, and peripheral blood mononuclear cells (PBMCs) were separated by using Ficoll. Using a flow cytometer, the frequency of CD4+HLA-G+ and CD8+ HLA-G+ T cells was assessed in the peripheral blood samples of primary unexplained infertile and fertile females. Our results showed that the frequency of CD8+HLA-G+ Treg cells was significantly lower in primary unexplained infertile females than fertile females (P = 0.048). Although the frequency of CD4+HLA-G+ Treg cells in the primary unexplained infertile females was lower than fertile females, the difference was not statistically significant (P = 0.25). Regarding the important role of CD8+HLA-G+ Treg cells during pregnancy and its decrease in females with primary UI, it seems that reduced CD8+ HLA-G+ Treg cells could be a leading immunological factor in the context of infertility. Nevertheless, more researches are needed in this field.

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References

  1. Ehsani M, Mohammadnia-Afrouzi M, Mirzakhani M, Esmaeilzadeh S, Shahbazi M. Female unexplained infertility: a disease with imbalanced adaptive immunity. J Hum Reprod Sci. 2019;12:274–82.

    Article  CAS  Google Scholar 

  2. Jasper MJ, Tremellen KP, Robertson SA. Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Mol Hum Reprod. 2006;12:301–8.

    Article  CAS  Google Scholar 

  3. Ozkan ZS, Deveci D, Kumbak B, Simsek M, Ilhan F, Sekercioglu S, et al. What is the impact of Th1/Th2 ratio, SOCS3, IL17, and IL35 levels in unexplained infertility? J Reprod Immunol. 2014;103:53–8.

    Article  CAS  Google Scholar 

  4. Carosella ED, Favier B, Rouas-Freiss N, Moreau P, Lemaoult J. Beyond the increasing complexity of the immunomodulatory HLA-G molecule. Blood. 2008;111:4862–70.

    Article  CAS  Google Scholar 

  5. Abediankenari S, Farzad F, Rahmani Z, Hashemi-Soteh MB. HLA-G5 and G7 isoforms in pregnant women. Iran J Allergy Asthm. 2015;14:217–21.

    Google Scholar 

  6. Hsu P, Santner-Nanan B, Joung S, Peek MJ, Nanan R. Expansion of CD4(+) HLA-G(+) T cell in human pregnancy is impaired in pre-eclampsia. Am J Reprod Immunol. 2014;71:217–28.

    Article  CAS  Google Scholar 

  7. Carosella ED, Gregori S, LeMaoult J. The tolerogenic interplay(s) among HLA-G, myeloid APCs, and regulatory cells. Blood. 2011;118:6499–505.

    Article  CAS  Google Scholar 

  8. Zare M, Namavar Jahromi B, Gharesi-Fard B. Analysis of the frequencies and functions of CD4(+)CD25(+)CD127(low/neg), CD4(+)HLA-G(+), and CD8(+)HLA-G(+) regulatory T cells in pre-eclampsia. J Reprod Immunol. 2019;133:43–51.

    Article  CAS  Google Scholar 

  9. Feger U, Tolosa E, Huang YH, Waschbisch A, Biedermann T, Melms A, et al. HLA-G expression defines a novel regulatory T-cell subset present in human peripheral blood and sites of inflammation. Blood. 2007;110:568–77.

    Article  CAS  Google Scholar 

  10. Shao L, Jacobs AR, Johnson VV, Mayer L. Activation of CD8+ regulatory T cells by human placental trophoblasts. J Immunol. 2005;174:7539–47.

    Article  CAS  Google Scholar 

  11. Tilburgs T, Roelen DL, van der Mast BJ, van Schip JJ, Kleijburg C, de Groot-Swings GM, et al. Differential distribution of CD4(+)CD25(bright) and CD8(+)CD28(−) T-cells in decidua and maternal blood during human pregnancy. Placenta. 2006;27(Suppl A):S47–53.

    Article  Google Scholar 

  12. Vianna P, Mondadori AG, Bauer ME, Dornfeld D, Chies JA. HLA-G and CD8+ regulatory T cells in the inflammatory environment of pre-eclampsia. Reproduction. 2016;152:741–51.

    Article  CAS  Google Scholar 

  13. Hill JA, Faris HMP, Schiff I, Anderson DJ. Characterization of leukocyte subpopulations in the peritoneal fluid of women with endometriosis. Fertil Steril. 1988;50:216–22.

    Article  CAS  Google Scholar 

  14. Steinborn A, Rebmann V, Scharf A, Sohn C, Grosse-Wilde H. Placental abruption is associated with decreased maternal plasma levels of soluble HLA-G. J Clin Immunol. 2003;23:307–14.

    Article  CAS  Google Scholar 

  15. LeMaoult J, Krawice-Radanne I, Dausset J, Carosella ED. HLA-G1-expressing antigen-presenting cells induce immunosuppressive CD4+ T cells. Proc Natl Acad Sci U S A. 2004;101:7064–9.

    Article  CAS  Google Scholar 

  16. Hu D, Chen Y, Zhang W, Wang H, Wang Z, Dong M. Alteration of peripheral CD4+CD25+ regulatory T lymphocytes in pregnancy and pre-eclampsia. Acta Obstet Gynecol Scand. 2008;87:190–4.

    Article  Google Scholar 

  17. Paeschke S, Chen F, Horn N, Fotopoulou C, Zambon-Bertoja A, Sollwedel A, et al. Pre-eclampsia is not associated with changes in the levels of regulatory T cells in peripheral blood. Am J Reprod Immunol. 2005;54:384–9.

    Article  Google Scholar 

  18. Sasaki Y, Darmochwal-Kolarz D, Suzuki D, Sakai M, Ito M, Shima T, et al. Proportion of peripheral blood and decidual CD4(+) CD25(bright) regulatory T cells in pre-eclampsia. Clin Exp Immunol. 2007;149:139–45.

    Article  CAS  Google Scholar 

  19. Prins JR, Boelens HM, Heimweg J, Van der Heide S, Dubois AE, Van Oosterhout AJ, et al. Preeclampsia is associated with lower percentages of regulatory T cells in maternal blood. Hypertens Pregnancy. 2009;28:300–11.

    Article  Google Scholar 

  20. Toldi G, Saito S, Shima T, Halmos A, Veresh Z, Vasarhelyi B Jr, et al. The frequency of peripheral blood CD4+ CD25high FoxP3+ and CD4+ CD25- FoxP3+ regulatory T cells in normal pregnancy and pre-eclampsia. Am J Reprod Immunol. 2012;68:175–80.

    Article  CAS  Google Scholar 

  21. Amodio G, Mugione A, Sanchez AM, Vigano P, Candiani M, Somigliana E, et al. HLA-G expressing DC-10 and CD4(+) T cells accumulate in human decidua during pregnancy. Hum Immunol. 2013;74:406–11.

    Article  CAS  Google Scholar 

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Funding

This study was financially supported by grantsfrom Babol University of Medical Sciences and Gerash University of Medical Sciences.

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The guarantor of integrity of entire study: MS; study concepts/study design: MS, MM, SE; data acquisition or data analysis/interpretation: all authors; manuscript drafting or manuscript revision for important intellectual content: MS, MM, ME; approval of the final version of the submitted manuscript: all authors.

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Correspondence to Mohammad Jafari or Mehdi Shahbazi.

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Ehsani, M., Mohammadnia-Afrouzi, M., Esmaeilzadeh, S. et al. Decreased Frequency of CD8+HLA-G+ T Cell in the Peripheral Blood of Primary Unexplained Infertile Females. Reprod. Sci. 28, 1939–1944 (2021). https://doi.org/10.1007/s43032-020-00431-z

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  • DOI: https://doi.org/10.1007/s43032-020-00431-z

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