Decidual Stromal Cells Promote Regulatory T Cells and Suppress Alloreactivity in a Cell Contact-Dependent Manner
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1
Karolinska Institutet, Sweden
We introduced the use of stromal cells from term fetal membrane (FMCs) in patients
with steroid refractory Graft-versus-host Disease. FMCs have many advantages
compared to bone marrow-derived mesenchymal stromal cells (BM-MSCs), including
an increased allosuppression, unlimited supply, great expansion potential and high
expression of integrins. In this study, we are elucidating factors of importance in the
reduction of alloreactivity by FMCs. We found that FMCs require cell-cell contact in
order to mediate suppression in mixed lymphocyte reactions (MLR) (p=0.01, n=11).
The frequency of CD4+CD25highFOXP3+ regulatory T-cells (Treg) was increased
(median 2.3-fold), whereas the proportion of total CD25+ T-cells was decreased
(median 1.4-fold) when the FMCs were added to the MLR cultures (p=0.03, n=10
and p=0.03, n=6, respectively). This was only observed when cell-cell contact was
allowed between the MLR and FMCs. Blocking activity of indoleamine-2,3-
dioxygenase (IDO) (median 2.6-fold increase in proliferation compared to
MLR+FMC-control, p=0.01, n=8), IFN-gamma (median 2.0-fold increase, p<0.01,
n=11), Prostaglandin E2 (median 1.26-fold increase, p=0.01, n=12) and PD-L1
(median 1.23-fold increase, p=0.03, n=7), significantly impaired the anti-proliferative
ability of the FMCs in MLRs. Inactivation of IDO reduced the frequency of Tregs. In
contrast to BM-MSC, pre-treatment of the FMCs with IFN-gamma (100 U/ml)
decreased suppression of alloreactivity (p<0.01, n=16), but stimulation of FMCs with
MLR supernatants containing low levels of IFN-gamma had no effect on the
suppressive capacity in the MLR.
To conclude, FMCs differs in several aspects from MSCs and needs proximity to
allo-reactive lymphocytes to mediate a suppressive effect and increase the frequency
of Tregs.
Keywords:
Decidual Stromal cells,
Mesenchymal Stromal Cells,
Stem Cell Transplantation,
Graft vs Host Disease,
regulatory T cells
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Erkers
T,
Nava
S,
Yosef
J,
Ringdén
O and
Kaipe
H
(2013). Decidual Stromal Cells Promote Regulatory T Cells and Suppress Alloreactivity in a Cell Contact-Dependent Manner.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00639
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Mr. Tom Erkers, Karolinska Institutet, Stockholm, Sweden, terkers@stanford.edu