Comparison of the percentages of CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia
Farha El-Chennawi
Clinical and Chemical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Search for more papers by this authorIbrahim Mohamed Rageh
Clinical and Chemical Pathology Department, Faculty of Medicine, Benha University, Benha, Egypt
Search for more papers by this authorCorresponding Author
Amira Ibrahim Mansour
Clinical and Chemical Pathology Department, Faculty of Medicine, Benha University, Benha, Egypt
Correspondence
Amira Ibrahim Mansour, Clinical and Chemical Pathology Department, Faculty of Medicine, Benha University, Benha, Egypt.
Emails: [email protected] and [email protected]
Search for more papers by this authorMohammed Ibrahim Darwish
Clinical and Chemical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Search for more papers by this authorAshraf Antar Elghzaly
Clinical and Chemical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Search for more papers by this authorBasma El Sayed Sakr
Gynecology and Obstetrics Department, Faculty of Medicine, Benha University, Benha, Egypt
Search for more papers by this authorKhaled Mohsen Elbaz
Faculty of Medicine, Benha University, Benha, Egypt
Search for more papers by this authorFarha El-Chennawi
Clinical and Chemical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Search for more papers by this authorIbrahim Mohamed Rageh
Clinical and Chemical Pathology Department, Faculty of Medicine, Benha University, Benha, Egypt
Search for more papers by this authorCorresponding Author
Amira Ibrahim Mansour
Clinical and Chemical Pathology Department, Faculty of Medicine, Benha University, Benha, Egypt
Correspondence
Amira Ibrahim Mansour, Clinical and Chemical Pathology Department, Faculty of Medicine, Benha University, Benha, Egypt.
Emails: [email protected] and [email protected]
Search for more papers by this authorMohammed Ibrahim Darwish
Clinical and Chemical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Search for more papers by this authorAshraf Antar Elghzaly
Clinical and Chemical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Search for more papers by this authorBasma El Sayed Sakr
Gynecology and Obstetrics Department, Faculty of Medicine, Benha University, Benha, Egypt
Search for more papers by this authorKhaled Mohsen Elbaz
Faculty of Medicine, Benha University, Benha, Egypt
Search for more papers by this authorAbstract
Problem
Little is known about how preeclampsia affects regulatory T-cell count and functions in umbilical cord blood of babies born to preeclamptic mothers. Here, we analyze the percentage of CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia.
Method of study
The percentage of umbilical cord blood CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs were analyzed by flow cytometry.
Results
CD4+ CD25high FOXP3+ Treg (%) and CD4+ FOXP3+ Treg (%) were significantly lower, while CD4+ CD25low (%) was significantly higher in umbilical cord blood of babies born to preeclamptic mothers.
Conclusion
Preeclampsia is associated with immune dysregulation which leads to a deficiency in Treg (CD4+ CD25high FOXP3+) in the umbilical cord blood of babies born to preeclamptic mothers.
REFERENCES
- 1Al-Jameil N, Khan FA, Khan MF, Tabassum H. A brief overview of preeclampsia. J Clin Med Res. 2014; 1: 1-7.
- 2Loewendorf AI, Nguyen TA, Yesayan MN, Kahn DA. Preeclampsia is characterized by fetal NK cell activation and a reduction in regulatory T cells. Am J Reprod Immunol. 2015; 74: 258-267.
- 3Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006; 367: 1066-1074.
- 4Norouzian M, Rahimzadeh M, Rajaee M, Arabpour F, Naderi N. FoxP3 gene promoter polymorphism affects susceptibility to preeclampsia. Hum Immunol. 2016; 77: 1232-1238.
- 5Rowe JH, Ertelt JM, Xin L, Way SS. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature. 2012; 490: 102.
- 6Trowsdale J, Betz AG. Mother's little helpers: mechanisms of maternal-fetal tolerance. Nat Immunol. 2006; 7: 241-246.
- 7Yoon SH, Hur M, Hwang HS, Kwon HS, Sohn IS. The difference of lymphocyte subsets including regulatory T-cells in umbilical cord blood between AGA neonates and SGA neonates. Yonsei Med J. 2015; 56: 798-804.
- 8Sharma S. Natural killer cells and regulatory T cells in early pregnancy loss. Int J Dev Biol. 2014; 58: 219.
- 9Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol. 2003; 4: 330-336.
- 10Miyara M, Yoshioka Y, Kitoh A, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity. 2009; 30: 899-911.
- 11La Rocca C, Carbone F, Longobardi S, Matarese G. The immunology of pregnancy: regulatory T cells control maternal immune tolerance toward the fetus. Immunol Lett. 2014; 162: 41-48.
- 12Sasaki Y, Darmochwal-Kolarz D, Suzuki D, et al. Proportion of peripheral blood and decidual CD4+ CD25bright regulatory T cells in pre-eclampsia. Clin Exp Immunol. 2007; 149: 139-145.
- 13Hsu P, Santner-Nanan B, Dahlstrom JE, et al. Altered decidual DC-SIGN+ antigen-presenting cells and impaired regulatory T-cell induction in preeclampsia. Am J Pathol. 2012; 181: 2149-2160.
- 14Steinborn A, Haensch GM, Mahnke K, et al. Distinct subsets of regulatory T cells during pregnancy: is the imbalance of these subsets involved in the pathogenesis of preeclampsia? Clin Immunol. 2008; 129: 401-412.
- 15Santner-Nanan B, Peek MJ, Khanam R, et al. Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia. J Immunol. 2009; 183: 7023-7030.
- 16Darmochwal-Kolarz D, Kludka-Sternik M, Tabarkiewicz J, et al. The predominance of Th17 lymphocytes and decreased number and function of Treg cells in preeclampsia. J Reprod Immunol. 2012; 93: 75-81.
- 17Toldi G, Rigo J, Stenczer B, Vásárhelyi B, Molvarec A. Increased prevalence of IL-17-producing peripheral blood lymphocytes in preeclampsia. Am J Reprod Immunol. 2011; 66: 223-229.
- 18Hafeez NA, Fouda MT, Abdel GE, Assar T, Mansour AI. The role of regulatory T cells in preeclampsia. Egypt J Immunol. 2013; 21: 45-55.
- 19Moreno-Eutimio MA, Tovar-Rodriguez JM, Vargas-Avila K, et al. Increased serum levels of inflammatory mediators and low frequency of regulatory T cells in the peripheral blood of preeclamptic Mexican women. Biomed Res Int. 2014; 2014. https://doi.org/10.1155/2014/413249.
- 20Ruocco MG, Chaouat G, Florez L, Bensussan A, Klatzmann D. Regulatory T-cells in pregnancy: historical perspective, state of the art, and burning questions. Front Immunol. 2014; 5: 389.
- 21Higgins JR, de Swiet M. Blood-pressure measurement and classification in pregnancy. Lancet. 2001; 357: 131-135.
- 22von Dadelszen P, Magee LA, Roberts JM. Subclassification of preeclampsia. Hypertens Pregnancy. 2003; 22: 143-148.
- 23Freeman DJ, McManus F, Brown EA, et al. Short- and long-term changes in plasma inflammatory markers associated with preeclampsia. Hypertension. 2004; 44: 708-714.
- 24Bassiouny MR, El-Chennawi F, Mansour AK, Yahia S, Darwish A. Optimal method for collection of umbilical cord blood: an Egyptian trial for a public cord blood bank. Transfusion. 2015; 55: 1263-1268.
- 25Zhao S, Gu Y, Dong Q, Fan R, Wang Y. Altered interleukin-6 receptor, IL-6R and gp130, production and expression and decreased SOCS-3 expression in placentas from women with preeclampsia. Placenta. 2008; 29: 1024-1028.
- 26Zenclussen ML, Thuere C, Ahmad N, et al. The persistence of paternal antigens in the maternal body is involved in regulatory T-cell expansion and fetal-maternal tolerance in murine pregnancy. Am J Reprod Immunol. 2010; 63: 200-208.
- 27Takahata Y, Nomura A, Takada H, et al. CD25+CD4+ T cells in human cord blood: an immunoregulatory subset with naive phenotype and specific expression of forkhead box p3 (Foxp3) gene. Exp Hematol. 2004; 32: 622-629.
- 28Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010; 10: 490-500.
- 29Mackroth MS, Malhotra I, Mungai P, Koech D, Muchiri E, King CL. Human cord blood CD4+CD25hi regulatory T cells suppress prenatally acquired T cell responses to Plasmodium falciparum antigens. J Immunol. 2011; 186: 2780-2791.
- 30Kim H, Moon HW, Hur M, et al. Distribution of CD4+ CD25 high FoxP3+ regulatory T-cells in umbilical cord blood. J Matern Fetal Neonatal Med. 2012; 25: 2058-2061.
- 31Prins JR, Boelens HM, Heimweg J, et al. Preeclampsia is associated with lower percentages of regulatory T cells in maternal blood. Hypertens Pregnancy. 2009; 28: 300-311.
- 32Levine RJ, Lam C, Qian C, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006; 355: 992-1005.
- 33Saito S. Th17 cells and regulatory T cells: new light on pathophysiology of preeclampsia. Immunol Cell Biol. 2010; 88: 615.
- 34Rahimzadeh M, Norouzian M, Arabpour F, Naderi N. Regulatory T-cells and preeclampsia: an overview of literature. Expert Rev Clin Immunol. 2016; 12: 209-227.
- 35Visser N, van Rijn BB, Rijkers GT, Franx A, Bruinse HW. Inflammatory changes in preeclampsia: current understanding of the maternal innate and adaptive immune response. Obstet Gynecol Surv. 2007; 62: 191-201.
- 36Toldi G, Vasarhelyi ZE, Rigo J, et al. Prevalence of regulatory T-cell subtypes in preeclampsia. Am J Reprod Immunol. 2015; 74: 110-115.
- 37Boij R, Mjosberg J, Svensson Arvelund J, et al. Regulatory T-cell subpopulations in severe or early-onset preeclampsia. Am J Reprod Immunol. 2015; 74: 368-378.
- 38Toldi G, Saito S, Shima T, 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: 175-180.
- 39Cerdeira AS, Kopcow HD, Karumanch SA. Regulatory T cells in preeclampsia. Some answers, more questions? AJP. 2012; 181: 1900-1902.
