Mesenchymal Stem Cells (MSC) are an interesting cell therapy for clinical organ transplantation and are usually isolated from bone marrow (BM-MSC) or adipose tissue (A-MSC) of either autologous or allogeneic origin. Allogeneic cell use seems convenient but might harbor the risk of sensitization against foreign HLA. Therefore, we evaluated whether BM-MSC and or A-MSC are capable of induction of HLA specific lysis by CD8+ T cells.
HLA class-I mismatched BM-MSC and A-MSC from healthy individuals were used in parallel experiments (n=5) as stimulators and targets. MSC were either stimulated with 50ng/ml IFNΓ or unstimulated before co-culture with IL-2 activated HLA class-I mismatched PBMC. Effector CD3+CD8+ T cells were obtained from these co-cultures via FACS sorting. Target BM-MSC and A-MSC were labeled with Europium and incubated for 4 hours with effector cells. Lysis was determined by measurement of Europium release.
Co-culture of PBMC and BM-MSC induced CD8+ T cells capable of lysing BM-MSC and not the mismatched A-MSC, showing that lysis was HLA class-I specific. The CD8+ mediated lysis increased when stimulator MSC and/or target MSC were IFNΓ-stimulated, which augmented HLA class-I expression, and ranged from a mean of 10.9% (effector: target (E:T) ratio 5:1) till 75.1% (E:T ratio 40:1) (figure 1).
Using A-MSC in the co-culture resulted in HLA class-I specific CD8+ mediated lysis of A-MSC. Yet, this effect was less prominent than for BM-MSC with a maximal mean lysis of 30.5% (E:T ratio 40:1) using IFNΓ-stimulated stimulator and target MSC.
Both BM-MSC and A-MSC can induce HLA class-I specific lysis by CD8+ T cells. These results indicate a potential risk of allogeneic MSC use of sensitization against HLA and plea in favor of autologous cell usage for clinical application.
To cite this abstract in AMA style:Rhijn MRoemeling-van, Reinders M, Franquesa M, Engela A, Korevaar S, Baan C, Roelofs H, IJzermans J, Betjes M, Weimar W, Hoogduijn M. Bone Marrow and Adipose Tissue Derived Mesenchymal Stem Cells Induce HLA-Specific Lysis by CD8+ T Cells [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/bone-marrow-and-adipose-tissue-derived-mesenchymal-stem-cells-induce-hla-specific-lysis-by-cd8-t-cells/. Accessed September 27, 2020.
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