Characteristics of T- and B-lymphocytes of blood at different stages of pregnancy and peculiarities of immunity in women with preeclampsia
Abstract
The study of immune mechanisms during pregnancy is an important area of research aimed at understanding the immunogenesis of pregnancy and its complications. One such complication is nephropathy, which requires accurate prediction of its course and appropriate therapy.
The present study aimed to assess the blood levels of T-lymphocytes (T-helper, T-suppressor/cytotoxic), B-lymphocytes, and markers of their activation in pregnant women, with a particular focus on patients with preeclampsia (PE).
Methods. Using a cellular cytofluorimeter and the corresponding test systems, we determined the relative levels of immunocompetent blood cells such as CD3+, CD4+, CD8+, CD19+-l with the expression of HLA-DR, CD25, CD5 activation markers in 436 non-pregnant women and 514 pregnant women. We analyzed the characteristics of these indicators at different stages of pregnancy, specifically before (1-4 groups) and after (5 group) 20 weeks. In the second stage, we performed an analysis of the indicators in 107 women with PE, 14 women after PE, and 54 pregnant women in the reference group without complications at 20+ weeks. This analysis included T- and B-cell studies of these patient groups under in vitro conditions with autoserum and inactivated serum.
Results. The first weeks of pregnancy were characterized by a high relative level (%) in the blood of T-l and subpopulations of T-h and Ts/c, as well as their activation according to the expression data of DR, CD25 (for CD4+-l), and CD5 (for CD19+-l). These indicators significantly decrease from 20 weeks of pregnancy and become comparable to the levels in non-pregnant women. The percentages of CD3+4+25+-l and CD19+5+-l are below the normal range, indicating a decrease in T-helper cell and B-cell activation during this period of pregnancy. In patients with PE after 20 weeks of pregnancy, the relative levels of T-l, B-l, T-h, and Ts/c did not differ from the reference group. Incubation of T- and B-l of women with PE with autoserum in vitro almost tripled the number of T- and B-l, and the blocking effect was greater than in women without PE, with a significant difference between them; the average ratio T-l/T-las exceeded the reference in the subgroup of active manifestations of PE.
Conclusion. Studying the relative levels of T-l, T-h, T-s/c, and B-l in the blood, as well as markers of their activation, at different stages of pregnancy with in vitro detection of features of the humoral immune response as predictors of NP allows determining individual components of immunogenetic and prognostic markers for personalized therapy during pregnancy.
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References
Aplin JD. The cell biology of human implantation. Placenta. 1996;17(5):269–275. doi: 10.1016/s0143-4004(96)90050-8.
Yu L, Zhang Y, Xiong J, Liu J, Zha Y, Kang Q, et al. Activated γδ T Cells With Higher CD107a Expression and Inflammatory Potential During Early Pregnancy in Patients With Recurrent Spontaneous Abortion. Front Immunol. 2021;12:724662. doi: 10.3389/fimmu.2021.724662.
Li D, Zheng L, Zhao D, Xu Y, Wang Y. The Role of Immune Cells in Recurrent Spontaneous Abortion. Reprod Sci. 2021; 28(12):3303-3315. doi: 10.1007/s43032-021-00599-y.
Terzieva A, Dimitrova V, Djerov L, Dimitrova P, Zapryanova S, Hristova I, et al. Early Pregnancy Human Decidua Is Enriched With Activated, Fully Differentiated and Pro-Inflammatory Gamma/Delta T Cells With Diverse TCR Repertoires. Int J Mol Sci.2019;20(3):687. doi: 10.3390/ijms20030687.
Zhu X, Zhu J. CD4 T Helper Cell Subsets and Related Human Immunological Disorders. Int. J. Mol. Sci. 2020;21:8011. doi: 10.3390/ijms21218011.
Piccinni MP, Lombardelli L, Logiodice F, Kullolli O, Romagnani S, Le Bouteiller P. T helper cell mediated-tolerance towards fetal allograft in successful pregnancy. Clin Mol Allergy. 2015;13:9. doi: 10.1186/s12948-015-0015-y.
Darmochwal-Kolarz D, Saito S, Rolinski J, Tabarkiewicz J, Kolarz B, Leszczynska-Gorzelak B, et al. Activated T lymphocytes in pre-eclampsia. Am J Reprod Immunol. 2007;58(1):39-45. doi: 10.1111/j.1600-0897.2007.00489.x.
Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA. D4+CD25high regulatory cells in human peripheral blood. J. Immunol. 2001;167(3):1245-53. doi: 10.4049/jimmunol.167.3.1245.
Saraiva M, Vieira P, O'Garra A. Biology and therapeutic potential of interleukin-10. J Exp Med. 2020;217(1). doi: 10.1084/jem.20190418.
Chatila TA. Role of regulatory T cells in human diseases. J. Allergy Clin. Immunol. 2005;116(5):949-59. doi: 10.1016/j.jaci.2005.08.047.
Duan B, Morel L. Role of B-1a cells in autoimmunity. Autoimmun Rev. 2006;5(6):403-8. doi:10.1016/j.autrev.2005.10.007.
Wanleenuwat P, Iwanowski P. Role of B cells and antibodies in multiple sclerosis. Mult Scler Relat Disord. 2019;36:101416. doi: 10.1016/j.msard.2019.101416.
Hippen KL, Tze LE, Behrens TW. CD5 maintains tolerance in anergic B cells. J Exp Med. 2000;191(5):883-90. doi:10.1084/jem.191.5.883.
Ishida D, Su L, Tamura A, Katayama Y, Kawai Y, Wang SF, et al. Rap1 signal controls B cell receptor repertoire and generation of self-reactive B-1a cells. Immunity.2006;24:417-27. doi: 10.1016/j.immuni.2006.02.007.
Nor Azlin M, Bakin YD, Mustafa N, Wahab NA, Johari MJ, Kamarudin NA, et al. Thyroid autoantibodies and associated complications during pregnancy. J Obstet Gynaecol. 2010;30:675-78. doi: 10.3109/01443615.2010.503908.
Do Prado AD, Piovesan DM, Staub HL, Horta BL. Association of anticardiolipin antibodies with preeclampsia: a systematic review and meta-analysis. Obstet Gynecol. 2010;116:1433-43. doi: 10.1097/AOG.0b013e3181fe02ec.
Yuling H, Ruijing X, Xiang J, Yanping J, Lang C, Li L, et al. CD19+CD5+ Bcells in primary IgA nephropathy. J Am Soc Nephrol. 2008; 19(11):2130-9. doi: 10.1681/ASN.2007121303.
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