alexa IFNGamma Priming Protects Fetal and Embryonic MSC from NK Cell-Mediated Killing and Improves their Immunosuppressive Properties: Role of Activating and Inhibitory Receptors
ISSN: 2157-7013

Journal of Cell Science & Therapy
Open Access

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Research Article

IFNGamma Priming Protects Fetal and Embryonic MSC from NK Cell-Mediated Killing and Improves their Immunosuppressive Properties: Role of Activating and Inhibitory Receptors

Giuliani M1*, Poggi A2, Bennaceur Griscelli A3,4,5 and Lataillade JJ1

1Research and Cell Therapy Department, Military Blood Trasfusion Centre (CTSA), Percy Military Hospital, Clamart, France

2Molecular Oncology and Angiogenesis Unit, Oncologic Integrated Therapies, IRCCS AOU San Martino-IST National Institute for Cancer Research Genoa, Italy

3UMR 935 INSERM, Human ES Core Facility, ES Team Paris Sud, Villejuif, France

4University Paris Sud 11, Faculty of Medicine Kremlin Bicêtre, France

5Division of Onco-Hematology, Paul Brousse Hospital, APHP Villejuif, France

*Corresponding Author:
Massimo Giuliani
Research and Cell Therapy Department
Military Blood Trasfusion Centre (CTSA)-Percy Military Hospital
Clamart, France
Tel: +33141467272
E-mail: [email protected]

Received date: April 15, 2014; Accepted date: April 19, 2014; Published date: May 01, 2014

Citation: Giuliani M, Poggi A, Bennaceur GA, Lataillade JJ (2014) IFNGamma Priming Protects Fetal and Embryonic MSC from NK Cell-Mediated Killing and Improves their Immunosuppressive Properties: Role of Activating and Inhibitory Receptors. J Cell Sci Ther 5:164. doi: 10.4172/2157-7013.1000164

Copyright: © 2014 Giuliani M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

The enhancement of Mesenchymal Stem Cells (MSC) immunosuppressing function can favour the engraftment of MSC employed in tissue repair. IFN-γ is a pro-inflammatory cytokine, which induces tolerogenic molecules in bone marrow (BM) MSC. We have investigated the interaction of IFN-γ primed MSC from fetal (FL-MSC) and embryonic (ES-MSC) origin with natural killer (NK) cells. IFN-γ -primed FL-/ES-MSC were less susceptible to NK cell-mediated killing, where a major role was played by the IFN-γ-induced up-regulation of HLA-ABC and HLA-E. Monoclonal antibody-mediated blocking of CD94/NKG2A on NK cells increased killing of IFN-γ-primed MSC, suggesting a role of this NK cell inhibitory receptor in MSC protection. NKG2D ligands (such as MICA), LFA-1 and ICAM1 expressed on MSC were also involved in NK cell-mediated killing of un-primed, but not of IFN-γ-primed, FL-/ES-MSC. Importantly, NK cells from IFN-γ-primed FL-/ES-MSC-NK cell co-cultures displayed a reduced intracellular free calcium increase, pERK activation, degranulation, cytolysis and IFN-γ production upon interaction with the NK sensitive target cell K562 compared to NK cells from un-primed FL/ES-MSC-NK cell co-cultures. Finally, PGE-2, increased during NK/MSC co-cultures, appeared to be a key soluble factor responsible for FL-/ES-MSC-mediated immunosuppressive effect. These results suggest that surface molecules such as MICA, HLA-E and ICAM1 can play a role in recognizing un-primed FL/ES-MSC but not IFN-γ-primed MSC where HLA-I is a key molecule for NK cellmediated recognition. Further, the strong immunosuppressive effect of IFN-γ-primed FL-/ES-MSC on NK cells could be exploited in cellular therapy protocols.

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