A Phenotypic Analysis of Regulatory T Cells and Uterine NK Cells from First Trimester Pregnancies and Associations with HLA-G

TY - JOUR

T1 - A Phenotypic Analysis of Regulatory T Cells and Uterine NK Cells from First Trimester Pregnancies and Associations with HLA-G

AU - Djurisic, Snezana

AU - Skibsted, Lillian

AU - Hviid, Thomas Vauvert F

N1 - © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2015/11

Y1 - 2015/11

N2 - PROBLEM: The prevalence of regulatory T cells and NK cells expressing activation and HLA-G receptors, and the influence of in vivo sHLA-G and mHLAG on HLA-G receptors expressed by NK cells in the uterine compartment is unclear.METHOD OF STUDY: KIR2DL4 and/or ILT2 expression on regulatory T cells and NK cells from the placental bed and peripheral blood in first trimester was assessed using flow cytometry. Expression of mHLA-G on trophoblast cells and sHLA-G in 'uterine' and peripheral blood was determined with ELISA and flow cytometry, and specific associations with expression levels of cognate receptors or activation markers on immune cells were determined.RESULTS: In the placental bed, CD45RA surface expression on Tregs was similar to peripheral Tregs in pregnant women, but T cells with lower CD4 and CD8 expression were accumulated. HLA-G receptor expression was increased on NK cells from 'uterine blood'. Soluble HLA-G was significantly increased in 'uterine blood' compared with peripheral blood, but no correlation was found between sHLA-G and mHLA-G in the uterine compartment. A correlation was found between sHLA-G and the fraction of KIR2DL4-positive NK cells in the uterine compartment, and a tendency was observed between mHLA-G and the fraction of ILT2-positive NK cells in the uterine compartment.CONCLUSION: The NK subset in the placental bed displays a unique phenotype that may be influenced by mHLA-G on trophoblast cells and locally accumulated sHLA-G in the uterus.

AB - PROBLEM: The prevalence of regulatory T cells and NK cells expressing activation and HLA-G receptors, and the influence of in vivo sHLA-G and mHLAG on HLA-G receptors expressed by NK cells in the uterine compartment is unclear.METHOD OF STUDY: KIR2DL4 and/or ILT2 expression on regulatory T cells and NK cells from the placental bed and peripheral blood in first trimester was assessed using flow cytometry. Expression of mHLA-G on trophoblast cells and sHLA-G in 'uterine' and peripheral blood was determined with ELISA and flow cytometry, and specific associations with expression levels of cognate receptors or activation markers on immune cells were determined.RESULTS: In the placental bed, CD45RA surface expression on Tregs was similar to peripheral Tregs in pregnant women, but T cells with lower CD4 and CD8 expression were accumulated. HLA-G receptor expression was increased on NK cells from 'uterine blood'. Soluble HLA-G was significantly increased in 'uterine blood' compared with peripheral blood, but no correlation was found between sHLA-G and mHLA-G in the uterine compartment. A correlation was found between sHLA-G and the fraction of KIR2DL4-positive NK cells in the uterine compartment, and a tendency was observed between mHLA-G and the fraction of ILT2-positive NK cells in the uterine compartment.CONCLUSION: The NK subset in the placental bed displays a unique phenotype that may be influenced by mHLA-G on trophoblast cells and locally accumulated sHLA-G in the uterus.

KW - Adult

KW - Antigens, CD

KW - Female

KW - HLA-G Antigens

KW - Humans

KW - Killer Cells, Natural

KW - Pregnancy

KW - Pregnancy Trimester, First

KW - Receptors, Immunologic

KW - Receptors, KIR2DL4

KW - T-Lymphocytes, Regulatory

KW - Trophoblasts

KW - Journal Article

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

U2 - 10.1111/aji.12421

DO - 10.1111/aji.12421

M3 - Journal article

C2 - 26293482

SN - 1046-7408

VL - 74

SP - 427

EP - 444

JO - Early pregnancy : biology and medicine : the official journal of the Society for the Investigation of Early Pregnancy

JF - Early pregnancy : biology and medicine : the official journal of the Society for the Investigation of Early Pregnancy

IS - 5

ER -