Lymphocyte Activation in the Development of Immune Tolerance in Women with Recurrent Pregnancy Loss
- PDF / 598,258 Bytes
- 11 Pages / 612 x 792 pts (letter) Page_size
- 40 Downloads / 195 Views
Lymphocyte Activation in the Development of Immune Tolerance in Women with Recurrent Pregnancy Loss L. V. Krechetova1, L. V. Vanko1, V. V. Vtorushina1, M. A. Nikolaeva1, E. V. Inviyaeva1,a*, and N. K. Tetruashvili1 1
National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of the Russian Federation, 117997 Moscow, Russia a email: [email protected] Received November 8, 2019 Revised March 20, 2020 Accepted March 20, 2020
Abstract—Association between lymphocyte activation and formation of immune tolerance, as well as pregnancy outcome, in the case of immunocytotherapy (ICT) was studied in women with idiopathic recurrent pregnancy loss (IRPL). The con tent and phenotypic characteristics of activated T lymphocytes and NK cells were investigated in the peripheral blood of IRPL patients with different pregnancy outcomes (pregnancy prolongation to the full term and habitual miscarriage). The fraction of activated cells in the subpopulation of cytotoxic T lymphocytes (CD3+CD8+/CD3+CD8+CD69+) before ICT was significantly lower in women who lost the pregnancy. After ICT, the fraction of these cells during weeks 56 of pregnancy in woman with miscarriage was higher than in women with pregnancy prolonged to the fullterm. Excessive content of acti vated cytotoxic lymphocytes can be a mechanism underlying impaired maternal immunotolerance to fetal alloantigens, which is a leading factor of early pregnancy loss. The obtained data confirm the involvement of activated Th17 cells and FOXP3+ Treg cells in the formation of tolerance to paternal antigens of the fetus. Comparison of the decrease in the frac tion of CD4+CD25highRORγt+ lymphocytes at the early gestation period (56 weeks) and significant upregulation of the IL17 production by in vitro stimulated whole blood cells in women with miscarriage with the same parameters in women with prolonged pregnancy suggested an imbalance between proinflammatory Th17 cells and Treg cells. No such imbalance in the content effector T lymphocytes was observed in women with the fullterm pregnancy. Taken together, our data indi cate an important role of gestational activation of lymphocytes in the formation of maternal immune response to fetal alloantigens necessary for the prolongation of pregnancy. DOI: 10.1134/S0006297920050077 Keywords: immunotolerance, recurrent pregnancy loss, immunocytotherapy, CD69 expression, T lymphocytes, NK cells
INTRODUCTION Tolerance to paternal antigens is an obligatory con dition for the normal course of pregnancy and a key fac tor of normal fetal development. It is established that sig nals from the fertilized oocyte (surface antigens and Abbreviations: AHR, aromatic hydrocarbon receptor; ICT, immunocytotherapy; IRPL, idiopathic recurrent pregnancy loss; FOXP3, forkhead box p3 protein (transcription factor reg ulating cell differentiation and expression of cytokine partici pating in immune response suppression); NK cell, natural killer cell; RORγt, retinoidrelated orphan receptor (transcription fact
Data Loading...
