Aberrant ICOS+ -T cell differentiation in women with spontaneous preterm labor

Am J Reprod Immunol. 2016 Nov;76(5):415-425. doi: 10.1111/aji.12565. Epub 2016 Sep 21.

Abstract

Problem: Recent studies revealed appropriate differentiation of recent thymic emigrant (RTE)-regulatory T cells (Tregs) to be crucial for maintaining healthy pregnancy. Currently, the role of responder T cells (Tresps) is not known.

Method of study: Six-color flow cytometric analysis was used to detect differences in the differentiation of highly proliferative inducible co-stimulatory (ICOS)+ -RTE-Tregs/Tresps and apoptosis-sensitive ICOS- -RTE-Tregs/Tresps into mature naïve (MN)-, CD31+ -memory and CD31- -memory Tregs/Tresps in women with spontaneous preterm labor (sPL) compared to healthy pregnancy.

Results: Healthy pregnancy was characterized by an increased differentiation of ICOS+ - and ICOS- -RTE-Tregs, as well as ICOS+ -RTE-Tresps via CD31+ -memory Tregs/Tresps into CD31- -memory Tregs/Tresps. Women with sPL showed an early interruption of RTE-Treg/Tresp differentiation. Instead, ICOS+ -MN-Tresps and partly ICOS- -MN-Tregs differentiated into CD31- -memory Tregs/Tresps, causing a significant reduction of both ICOS+ -Tregs and ICOS+ -Tresps, but an increase of ICOS- -Tresps within total CD4+ -T-helper cells.

Conclusion: Aberrant differentiation of ICOS+ -T cells is associated with sPL.

Keywords: cervical insufficiency; immunosuppression; pregnancy; preterm labor; preterm premature rupture of fetal membranes; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Differentiation
  • Cell Separation
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Humans
  • Immune Tolerance
  • Immunologic Memory
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Lymphocyte Activation
  • Obstetric Labor, Premature / immunology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Pregnancy
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Thymus Gland / immunology*
  • Young Adult

Substances

  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein
  • Platelet Endothelial Cell Adhesion Molecule-1