title: Human Allogeneic Bone Marrow and Adipose Tissue Derived Mesenchymal Stromal Cells Induce CD8+ Cytotoxic T Cell Reactivity.
abstract: BACKGROUND
  For clinical applications, Mesenchymal Stromal Cells (MSC) can be isolated from bone marrow and adipose tissue of autologous or allogeneic origin. Allogeneic cell usage has advantages but may harbor the risk of sensitization against foreign HLA. Therefore, we evaluated whether bone marrow and adipose tissue-derived MSC are capable of inducing HLA-specific alloreactivity.
  
  
  METHODS
  MSC were isolated from healthy human Bone Marrow (BM-MSC) and adipose tissue (ASC) donors. Peripheral Blood Mononuclear Cells (PBMC) were co-cultured with HLA-AB mismatched BM-MSC or ASC precultured with or without IFNy. After isolation via FACS sorting, the educated CD8+ T effector populations were exposed for 4 hours to Europium labeled MSC of the same HLA make up as in the co-cultures or with different HLA. Lysis of MSC was determined by spectrophotometric measurement of Europium release.
  
  
  RESULTS
  CD8+ T cells educated with BM-MSC were capable of HLA specific lysis of BM-MSC. The maximum lysis was 24% in an effector:target (E:T) ratio of 40:1. Exposure to IFNγ increased HLA-I expression on BM-MSC and increased lysis to 48%. Co-culturing of PBMC with IFNγ-stimulated BM-MSC further increased lysis to 76%. Surprisingly, lysis induced by ASC was significantly lower. CD8+ T cells educated with ASC induced a maximum lysis of 13% and CD8+ T cells educated with IFNγ-stimulated ASC of only 31%.
  
  
  CONCLUSIONS
  Allogeneic BM-MSC, and to a lesser extend ASC, are capable of inducing HLA specific reactivity. These results should be taken into consideration when using allogeneic MSC for clinical therapy.
authors.affiliation: Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Roemeling-van Rhijn
authors.affiliation: Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marlies E
authors.initials: ME
authors.lastname: Reinders
authors.affiliation: Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Marcella
authors.initials: M
authors.lastname: Franquesa
authors.affiliation: Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Anja U
authors.initials: AU
authors.lastname: Engela
authors.affiliation: Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Sander S
authors.initials: SS
authors.lastname: Korevaar
authors.affiliation: Immunohematology and bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Helene
authors.initials: H
authors.lastname: Roelofs
authors.affiliation: Department of Biology, University of York, York, United Kingdom.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Genever
authors.affiliation: General Surgery, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Jan Nm
authors.initials: JN
authors.lastname: Ijzermans
authors.affiliation: Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Michiel Gh
authors.initials: MG
authors.lastname: Betjes
authors.affiliation: Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
authors.affiliation: Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.affiliation: Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hoogduijn
keywords: Adipose tissue; Alloreactivity; Bone marrow; CD8+ cytotoxicity; HLA class I; Mesenchymal stromal cells
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