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

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

Kälble F ，Mai C ，Wagner M ，Schober L ，Schaier M ，Zeier M ，Spratte J ，Fluhr H ，Steinborn A ... -  《-》

Impaired Differentiation of Highly Proliferative ICOS(+)-Tregs Is Involved in the Transition from Low to High Disease Activity in Systemic Lupus Erythematosus (SLE) Patients.

Kälble F ，Wu L ，Lorenz HM ，Zeier M ，Schaier M ，Steinborn A ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Immunosuppressive therapy influences the accelerated age-dependent T-helper cell differentiation in systemic lupus erythematosus remission patients.

Schaier M ，Gottschalk C ，Uhlmann L ，Speer C ，Kälble F ，Eckstein V ，Müller-Tidow C ，Meuer S ，Mahnke K ，Lorenz HM ，Zeier M ，Steinborn A ... -  《-》

The role of age-related T-cell differentiation in patients with renal replacement therapy.

Schaier M ，Leick A ，Uhlmann L ，Kälble F ，Eckstein V ，Ho A ，Meuer S ，Mahnke K ，Sommerer C ，Zeier M ，Steinborn A ... -  《-》

Differentiation of ICOS+ and ICOS- recent thymic emigrant regulatory T cells (RTE T regs) during normal pregnancy, pre-eclampsia and HELLP syndrome.

Two different subsets of naturally occurring regulatory T cells (nTregs), defined by their expression of the inducible co-stimulatory (ICOS) molecule, are produced by the human thymus. To examine the differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) recent thymic emigrant (RTE) T regs during normal pregnancy and in the presence of pre-eclampsia or haemolysis elevated liver enzymes low platelet (HELLP)-syndrome, we used six-colour flow cytometric analysis to determine the changes in the composition of the ICOS(+) and ICOS(-) T reg pools with CD45RA(+) CD31(+) RTE T regs, CD45RA(+) CD31(-) mature naive (MN) T regs, CD45RA(-) CD31(+) and CD45RA(-) CD31(-) memory Tregs. With the beginning of pregnancy until term, we observed a strong differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE, but not CD45RA(+) CD31(-) MN T regs, into CD45RA(-) CD31(-) memory T regs. At the end of pregnancy, the onset of spontaneous term labour was associated with a significant breakdown of ICOS(+) CD45RA(-) CD31(-) memory T regs. However, in the presence of pre-eclampsia, there was a significantly increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs into CD45RA(-) CD31(+) memory T regs, wherein the lacking differentiation into CD45RA(-) CD31(-) memory T regs was partially replaced by the increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(-) MN Tregs into CD45RA(-) CD31(-) memory T regs. In patients with HELLP syndrome, this alternatively increased differentiation of CD45RA(-) CD31(-) MN T regs seemed to be exaggerated, and presumably restored the suppressive activity of magnetically isolated ICOS(+) and ICOS(-) T regs, which were shown to be significantly less suppressive in pre-eclampsia patients, but not in HELLP syndrome patients. Hence, our findings propose that the regular differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs ensures a healthy pregnancy course, while their disturbed differentiation is associated with the occurrence of pre-eclampsia and HELLP syndrome.

Wagner MI ，Jöst M ，Spratte J ，Schaier M ，Mahnke K ，Meuer S ，Zeier M ，Steinborn A ... -  《-》