American Journal of Reproductive Immunology

Volume 68, Issue 2 pp. 100-106

Original Article

An Increase of Treg Cells in the Peripheral Blood is Associated with a Better In Vitro Fertilization Treatment Outcome

Jianjun Zhou,

Jianjun Zhou

Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Search for more papers by this author

Zhiqun Wang,

Zhiqun Wang

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Search for more papers by this author

Xia Zhao,

Xia Zhao

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Search for more papers by this author

Junxia Wang,

Junxia Wang

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Search for more papers by this author

Haixiang Sun,

Haixiang Sun

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Search for more papers by this author

Yali Hu,

Corresponding Author

Yali Hu

Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Correspondence

Yali Hu, Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, 321 Zhong Shan Road, Nanjing 210008, China.

E-mail: [email protected]

Search for more papers by this author

Jianjun Zhou,

Jianjun Zhou

Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Search for more papers by this author

Zhiqun Wang,

Zhiqun Wang

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Search for more papers by this author

Xia Zhao,

Xia Zhao

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Search for more papers by this author

Junxia Wang,

Junxia Wang

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Search for more papers by this author

Haixiang Sun,

Haixiang Sun

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Search for more papers by this author

Yali Hu,

Corresponding Author

Yali Hu

Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Correspondence

Yali Hu, Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, 321 Zhong Shan Road, Nanjing 210008, China.

E-mail: [email protected]

Search for more papers by this author

First published: 12 June 2012

https://doi.org/10.1111/j.1600-0897.2012.01153.x

Citations: 70

Share a link

Email
Wechat
Bluesky

Abstract

Problem

The objective of this study was to determine whether there was any association between the peripheral blood CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells (Treg cells) and implantation success in patients undergoing in vitro fertilization (IVF) treatment.

Method of study

Prospective observational study of 101 randomly selected women who underwent IVF treatment for tubal factor from May 2011 to June 2011. The percentage of peripheral blood Treg cells and the expression levels of Foxp3 and CTLA4 mRNA in peripheral blood mononuclear cells (PBMCs) were recorded and their relations to IVF treatment outcomes were analyzed.

Results

Treg cells were significantly elevated in the pregnant group ( P = 0.03). The expression level of Foxp3 mRNA in PBMCs from pregnant group also significantly increased ( P = 0.02). A receiver operating characteristic analysis (area under curve = 0.631) found that those women with Treg cells >0.6%, the pregnancy rate and live birth rate were much higher as compared to women with Treg cells below this level ( P < 0.05). An increase of Treg cells in the peripheral blood was associated with a better IVF treatment outcome (OR 4.3, 95% CI = 1.76–10.48), with a sensitivity of 64%, specificity of 71%.

Conclusion

An elevated level of circulating Treg cells was associated with increased rates of pregnancy and live birth in IVF treatment.

References

1 Noronha LE, Antczak DF: Maternal immune responses to trophoblast: the contribution of the horse to pregnancy immunology. Am J Reprod Immunol 2010; 64: 231–244.
10.1111/j.1600-0897.2010.00895.x
PubMed Web of Science® Google Scholar
2 Guerin LR, Prins JR, Robertson SA: Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum Reprod Update 2009; 15: 517–535.
10.1093/humupd/dmp004
CAS PubMed Web of Science® Google Scholar
3 von Rango U: Fetal tolerance in human pregnancy–a crucial balance between acceptance and limitation of trophoblast invasion. Immunol Lett 2008; 115: 21–32.
10.1016/j.imlet.2007.09.014
CAS PubMed Web of Science® Google Scholar
4 He Q, Fan H, Li JQ, Qi HZ: Decreased circulating CD4 + CD25highFoxp3 + T cells during acute rejection in liver transplant patients. Transplant Proc 2011; 43: 1696–1700.
10.1016/j.transproceed.2011.03.084
CAS PubMed Web of Science® Google Scholar
5 Lourenço EV, La Cava A: Natural regulatory T cells in autoimmunity. Autoimmunity 2011; 44: 33–42.
10.3109/08916931003782155
CAS PubMed Web of Science® Google Scholar
6 Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S: Decidual and peripheral blood CD4 + CD25 + regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod 2004; 10: 347–353.
10.1093/molehr/gah044
CAS PubMed Web of Science® Google Scholar
7 Shevach EM, McHugh RS, Piccirillo CA, Thornton AM: Control of T-cell activation by CD4 + CD25 + suppressor T cells. Immunol Rev 2001; 182: 58–67.
10.1034/j.1600-065X.2001.1820104.x
CAS PubMed Web of Science® Google Scholar
8 Mjösberg J, Berg G, Ernerudh J, Ekerfelt C: CD4 + CD25 + regulatory T cells in human pregnancy: development of a Treg-MLC-ELISPOT suppression assay and indications of paternal specific Tregs. Immunology 2007; 120: 456–466.
10.1111/j.1365-2567.2006.02529.x
CAS PubMed Web of Science® Google Scholar
9 Pesu M, Watford WT, Wei L, Xu L, Fuss I, Strober W, Andersson J, Shevach EM, Quezado M, et al.: T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance. Nature 2008; 455: 246–250.
10.1038/nature07210
CAS PubMed Web of Science® Google Scholar
10 van der Vliet HJ, Nieuwenhuis EE: IPEX as a result of mutations in FOXP3. Clin Dev Immunol 2007; 2007: 89017.
10.1155/2007/89017
PubMed Web of Science® Google Scholar
11 Sun L, Wu J, Yi S: Foxp3 is critical for human natural CD4 + CD25 + regulatory T cells to suppress alloimmune response. Transpl Immunol 2011; 26: 71–80.
10.1016/j.trim.2011.10.005
CAS PubMed Web of Science® Google Scholar
12 Salama AK, Hodi FS: Cytotoxic T-lymphocyte-associated antigen-4. Clin Cancer Res 2011; 17: 4622–4628.
10.1158/1078-0432.CCR-10-2232
CAS PubMed Web of Science® Google Scholar
13 Vacchio MS, Jiang SP: The fetus and the maternal immune system: pregnancy as a model to study peripheral T-cell tolerance. Crit Rev Immunol 1999; 19: 461–480.
CAS PubMed Web of Science® Google Scholar
14 Thum MY, Bhaskaran S, Abdalla HI, Ford B, Sumar N, Shehata H, Bansal AS: An increase in the absolute count of CD56dimCD16 + CD69 + NK cells in the peripheral blood is associated with a poorer IVF treatment and pregnancy outcome. Hum Reprod 2004; 19: 2395–2400.
10.1093/humrep/deh378
CAS PubMed Web of Science® Google Scholar
15 King K, Smith S, Chapman M, Sacks G: Detailed analysis of peripheral blood natural killer (NK) cells in women with recurrent miscarriage. Hum Reprod 2010; 25: 52–58.
10.1093/humrep/dep349
CAS PubMed Web of Science® Google Scholar
16 Yamada H, Morikawa M, Kato EH, Shimada S, Kobashi G, Minakami H: Pre-conceptional natural killer cell activity and percentage as predictors of biochemical pregnancy and spontaneous abortion with normal chromosome karyotype. Am J Reprod Immunol 2003; 50: 351–354.
10.1034/j.1600-0897.2003.00095.x
CAS PubMed Web of Science® Google Scholar
17 Arruvito L, Sanz M, Banham AH, Fainboim L: Expansion of CD4 + CD25 + and FOXP3 + regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction. J Immunol 2007; 178: 2572–2578.
10.4049/jimmunol.178.4.2572
CAS PubMed Web of Science® Google Scholar
18 Wang WJ, Hao CF, Qu QL, Wang X, Qiu LH, Lin QD: The deregulation of regulatory T cells on interleukin-17-producing T helper cells in patients with unexplained early recurrent miscarriage. Hum Reprod 2010; 25: 2591–2596.
10.1093/humrep/deq198
CAS PubMed Web of Science® Google Scholar
19 Winger EE, Reed JL: Low circulating CD4(+) CD25(+) Foxp3(+) T regulatory cell levels predict miscarriage risk in newly pregnant women with a history of failure. Am J Reprod Immunol 2011; 66: 320–328.
10.1111/j.1600-0897.2011.00992.x
CAS PubMed Web of Science® Google Scholar
20 Jianjun Z, Yali H, Zhiqun W, Mingming Z, Xia Z: Imbalance of T-cell transcription factors contributes to the Th1 type immunity predominant in pre-eclampsia. Am J Reprod Immunol 2010; 63: 38–45.
10.1111/j.1600-0897.2009.00763.x
CAS PubMed Web of Science® Google Scholar
21 Tilburgs T, Roelen DL, van der Mast BJ, de Groot-Swings GM, Kleijburg C, Scherjon SA, Claas FH: Evidence for a selective migration of fetus-specific CD4 + CD25bright regulatory T cells from the peripheral blood to the decidua in human pregnancy. J Immunol 2008; 180: 5737–5745.
10.4049/jimmunol.180.8.5737
CAS PubMed Web of Science® Google Scholar
22 Gavin MA, Rasmussen JP, Fontenot JD, Vasta V, Manganiello VC, Beavo JA, Rudensky AY: Foxp3-dependent programme of regulatory T-cell differentiation. Nature 2007; 445: 771–775.
10.1038/nature05543
CAS PubMed Web of Science® Google Scholar
23 Salomon B, Bluestone JA: Complexities of CD28/B7:CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 2001; 19: 225–252.
10.1146/annurev.immunol.19.1.225
CAS PubMed Web of Science® Google Scholar
24 Luo CY, Wang L, Sun C, Li DJ: Estrogen enhances the functions of CD4(+)CD25(+)Foxp3(+) regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro. Cell Mol Immunol 2011; 8: 50–58.
10.1038/cmi.2010.54
CAS PubMed Web of Science® Google Scholar
25 Mao G, Wang J, Kang Y, Tai P, Wen J, Zou Q, Li G, Ouyang H, Xia G, et al.: Progesterone increases systemic and local uterine proportions of CD4+CD25+ Treg cells during midterm pregnancy in mice. Endocrinology 2010; 151: 5477–5488.
10.1210/en.2010-0426
CAS PubMed Web of Science® Google Scholar
26 Schumacher A, Brachwitz N, Sohr S, Engeland K, Langwisch S, Dolaptchieva M, Alexander T, Taran A, Malfertheiner SF, et al.: Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy. J Immunol 2009; 182: 5488–5497.
10.4049/jimmunol.0803177
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume68, Issue2

August 2012

Pages 100-106

An Increase of Treg Cells in the Peripheral Blood is Associated with a Better In Vitro Fertilization Treatment Outcome

Abstract

Problem

Method of study

Results

Conclusion

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

An Increase of Treg Cells in the Peripheral Blood is Associated with a Better In Vitro Fertilization Treatment Outcome

Abstract

Problem

Method of study

Results

Conclusion

References

Citing Literature

References

Related

Information