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

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.