Characterization of cord blood CD3+ TCRVα7.2+ CD161high T and innate lymphoid cells in the pregnancies with gestational diabetes, morbidly adherent placenta, and pregnancy hypertension diseases

Yesim Haliloglu; Alper Ozcan; Serife Erdem; Zehra Busra Azizoglu; Ayten Bicer; Ozcan Yeniay Ozarslan; Omer Kilic; Fatma Zehra Okus; Fatma Demir; Halit Canatan; Musa Karakukcu; Semih Zeki Uludag; M Serdar Kutuk; Ekrem Unal; Ahmet Eken

doi:10.1111/aji.13555

Characterization of cord blood CD3⁺ TCRVα7.2⁺ CD161^high T and innate lymphoid cells in the pregnancies with gestational diabetes, morbidly adherent placenta, and pregnancy hypertension diseases

Am J Reprod Immunol. 2022 Jul;88(1):e13555. doi: 10.1111/aji.13555. Epub 2022 May 1.

Authors

Yesim Haliloglu^{1

2}, Alper Ozcan³, Serife Erdem^{1

2}, Zehra Busra Azizoglu^{1

2}, Ayten Bicer^{1

2}, Ozcan Yeniay Ozarslan^{1

2}, Omer Kilic^{1

2}, Fatma Zehra Okus^{1

2}, Fatma Demir^{1

2}, Halit Canatan^{1

2}, Musa Karakukcu³, Semih Zeki Uludag⁴, M Serdar Kutuk⁵, Ekrem Unal^{2

3

6}, Ahmet Eken^{1

2}

Affiliations

¹ Department of Medical Biology, School of Medicine, Erciyes University, Kayseri, Turkey.
² Betül-Ziya Eren Genome and Stem Cell Center (GENKOK), Kayseri, Turkey.
³ Department of Pediatrics, Division of Pediatric Hematology and Oncology, School of Medicine, Erciyes University, Kayseri, Turkey.
⁴ Department of Obstetrics and Gynecology, School of Medicine, Erciyes University, Kayseri, Turkey.
⁵ Department of Obstetrics and Gynecology, School of Medicine, Bezmi Alem University, Istanbul, Turkey.
⁶ Department of Blood Banking and Transfusion Medicine, Health Science Institution, Erciyes University, Kayseri, Turkey.

PMID: 35452164
DOI: 10.1111/aji.13555

Abstract

Problem: Although pregnant women with gestational diabetes (GD), morbidly adherent placenta (MAP), and pregnancy hypertension (pHT) diseases lead to intrauterine growth restriction (IUGR), little is known about their effect on mucosal-associated invariant T (MAIT) and innate lymphoid cells (ILC) in the umbilical cord. This study aimed to quantify and characterize MAIT cells and ILCs in the cord blood of pregnant women with GD, MAP, and pHT diseases.

Method of study: Cord blood mononuclear cells (CBMCs) were isolated by Ficoll-Paque gradient. CD3⁺ TCRVα7.2⁺ CD161^high cells and ILC subsets were quantified by flow cytometry. CBMCs were stimulated with PMA/Ionomycin and Golgi Plug for 4 h and stained for IFN-γ, TNF-α, and granzyme B. The stained cells were analyzed on FACS ARIA III.

Results: Compared with healthy pregnancies, in the cord blood of the pHT group, elevated number of lymphocytes was observed. Moreover, the absolute number of IFN-γ producing CD4⁺ or CD4^- subsets of CD3⁺ TCRVα7.2⁺ CD161^high cells as well as those producing granzyme B were significantly elevated in the pHT group compared to healthy controls suggesting increased MAIT cell activity in the pHT cord blood. Similarly, in the MAP group, the absolute number of total CD3⁺ TCRVα7.2⁺ CD161^high cells, but not individual CD4⁺ or negative subsets, were significantly increased compared with healthy controls' cord blood. Absolute numbers of total CD3⁺ TCRVα7.2⁺ CD161^high cells and their subsets were comparable in the cord blood of the GD group compared with healthy controls. Finally, the absolute number of total ILCs and ILC3 subset were significantly elevated in only pHT cord blood compared with healthy controls. Our data also reveal that IFN-γ⁺ or granzyme B⁺ cell numbers negatively correlated with fetal birth weight.

Conclusions: CD3⁺ TCRVα7.2⁺ CD161^high cells and ILCs show unique expansion and activity in the cord blood of pregnant women with distinct diseases causing IUGR and may play roles in fetal growth restriction.

Keywords: Cord blood; ILC; IUGR; MAIT; diabetes; hypertension; morbidly adherent placenta.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes, Gestational* / immunology
Female
Fetal Blood / cytology
Fetal Blood / immunology
Granzymes
Humans
Hypertension, Pregnancy-Induced* / immunology
Immunity, Innate
Lymphocytes
Placenta / pathology
Placenta Accreta* / immunology
Pregnancy
T-Lymphocyte Subsets* / cytology

Substances

Granzymes