Title: Clinical-Grade Human Multipotent Adult Progenitor Cells Block CD8+ Cytotoxic T Lymphocytes
Authors: Plessers, Jeroen ×
Dekimpe, Emily
Van Woensel, Matthias
Roobrouck VD, Valerie
Bullens, Dominique
Pinxteren, Jef
Verfaillie, Catherine
Van Gool, Stefaan W #
Issue Date: Jul-2016
Publisher: AlphaMed Press, Inc
Series Title: Stem Cells Translational Medicine vol:Ahead of print
Article number: sctm.2016-0030
Abstract: : MultiStem cells are clinical-grade multipotent adult bone marrow-derived progenitor cells (MAPCs), with extensive replication potential and broader differentiation capacity compared with mesenchymal stem cells. Human MAPCs suppress T-cell proliferation induced by alloantigens and mutually interact with allogeneic natural killer cells. In this study, the interaction between MultiStem and CD8(+) cytotoxic T lymphocytes (CTLs) was addressed for the first time. In an in vitro setting, the immunogenicity of MultiStem, the susceptibility of MultiStem toward CTL-mediated lysis, and its effects on CTL function were investigated. MultiStem was nonimmunogenic for alloreactive CTL induction and was-even after major histocompatibility complex class I upregulation-insensitive to alloantigen-specific CTL-mediated lysis. Furthermore, MultiStem reduced CTL proliferation and significantly decreased perforin expression during the T-cell activation phase. As a consequence, MultiStem dose-dependently impaired the induction of CTL function. These effects of MultiStem were mediated predominantly through contact-dependent mechanisms. Moreover, MultiStem cells considerably influenced the expression of T-cell activation markers CD25, CD69, and human leukocyte antigen-DR. The MultiStem-induced CD8(-)CD69(+) T-cell population displayed a suppressive effect on the induction of CTL function during a subsequent mixed-lymphocyte culture. Finally, the killer activity of activated antigen-specific CTLs during their cytolytic effector phase was also diminished in the presence of MultiStem. This study confirms that these clinical-grade MAPCs are an immune-modulating population that inhibits CTL activation and effector responses and are, consequently, a highly valuable cell population for adoptive immunosuppressive therapy in diseases where damage is induced by CTLs.
ISSN: 2157-6564
Publication status: accepted
KU Leuven publication type: IT
Appears in Collections:Embryo and Stemcells (-)
Laboratory of Pediatric Immunology
Research Group Experimental Neurosurgery and Neuroanatomy
Stem Cell Biology and Embryology (+)
× corresponding author
# (joint) last author

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