Mesenchymal Stromal Cells Protect Endothelial Cells from Cytotoxic T Lymphocyte-Induced Lysis

Title: Mesenchymal Stromal Cells Protect Endothelial Cells from Cytotoxic T Lymphocyte-Induced Lysis
Authors: Cahill, Emer Frances
Sax, Tanja
Hartmann, Isabel
Kolch, Walter
Eissner, Günther
et al.
Permanent link: http://hdl.handle.net/10197/9122
Date: 24-Aug-2016
Abstract: The integrity of the vasculature plays an important role in the success ofallogeneic organ and haematopoietic stem cell transplantation. Endothelial cells(EC) have previously been shown to be the target of activated cytotoxic Tlymphocytes (CTL) resulting in extensive cell lysis. Mesenchymal stromal cells(MSC) are multipotent cells which can be isolated from multiple sites, eachdemonstrating immunomodul atory capabilities. They are explored herein fortheir potential to protect EC from CTL-targeted lys is. CD8+T cells isolated fromhuman PBMC were stimulated with mitotically inactive cells of a humanmicrovascular endothelial cell line (CDC/EU.HMEC-1, further referred to asHMEC) for 7 days. Target HMEC were cultured in the presence or absence ofMSC for 24 h before exposure to activated allogeneic CTL for 4 h. EC were thenanalysed for cytotoxic lysis by flow cytometry. Culture of HMEC with MSC inthe efferent immune phase (24 h before the assay) led to a decrease in HMEClysis. This lysis was determined to be MHC Class I restricted linked and furtheranalysis suggested that MSC contact is important in abrogation of lysis, asprotection is reduced where MSC are separated in transwell experiments. Theefficacy of multiple sources of MSC was also confirmed, and the collaborativeeffect of MSC and the endothelium protective drug defibrotide were determined,with defibrotide enhancing the protection provided by MSC. These resultssupport the use of MSC as an adjuvant cellular therapeutic in transplantmedicine, alone or in conjunction with EC protective agents such as defibrotide.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: Wiley
Copyright (published version): 2016 the Foundation for the Scandanavian Journal of Immunology
Keywords: Mesenchymal stromal cellsEndothelial cells
DOI: 10.1111/sji.12459
Language: en
Status of Item: Peer reviewed
Appears in Collections:SBI Research Collection

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