Human graft-derived mesenchymal stromal cells potently suppress alloreactive T-cell responses

Stem Cells and Development
Emmy L D de Mare-BredemeijerLuc J W van der Laan

Abstract

After organ transplantation, recipient T cells contribute to graft rejection. Mesenchymal stromal cells from the bone marrow (BM-MSCs) are known to suppress allogeneic T-cell responses, suggesting a possible clinical application of MSCs in organ transplantation. Human liver grafts harbor resident populations of MSCs (L-MSCs). We aimed to determine the immunosuppressive effects of these graft-derived MSCs on allogeneic T-cell responses and to compare these with the effects of BM-MSCs. BM-MSCs were harvested from aspirates and L-MSCs from liver graft perfusates. We cultured them for 21 days and compared their suppressive effects with the effects of BM-MSCs on allogeneic T-cell responses. Proliferation, cytotoxic degranulation, and interferon-gamma production of alloreactive T cells were more potently suppressed by L-MSCs than BM-MSCs. Suppression was mediated by both cell-cell contact and secreted factors. In addition, L-MSCs showed ex vivo a higher expression of PD-L1 than BM-MSCs, which was associated with inhibition of T-cell proliferation and cytotoxic degranulation in vitro. Blocking PD-L1 partly abrogated the inhibition of cytotoxic degranulation by L-MSCs. In addition, blocking indoleamine 2,3-dioxygenase partly abrogated ...Continue Reading

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Citations

Apr 27, 2016·Immunologic Research·Wancheng ChenYang Xiao
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Methods Mentioned

BETA
density gradient centrifugation
enzyme-linked immunosorbent assay
ELISA
flow cytometry
PCR

Software Mentioned

FlowJo
FACSDiva
ModFit
GraphPad Prism
ModFit LT
FlowJo Star

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