A paradoxical role for IFN-gamma in the immune properties of mesenchymal stem cells during viral challenge.
OBJECTIVE
The functional "plasticity" and immune-suppressive effects of human bone marrow (BM)-derived mesenchymal stem cells (MSC) provide them with the potential to be used across allogeneic barriers. The immunosuppressive properties of MSC may be detrimental in a clinical setting in which viral exposure is common. The study hypothesizes that MSC-derived IFN-gamma could offset the immune-suppressive functions of MSC and mediate partial CTL responses during viral infection.


METHODS
CTL responses were studied in bioassays with (51)Cr-P815 targets and PBMC (uninfected or infected) as effectors. Immunofluorescence studied the relative expression of CD8(+) cells. Cytokine analyses were performed with microarrays. Roles for IFN-gamma in CTL responses were studied with IFNgammaRI mAb or with MSC knockdown for IFN-gamma by siRNA (pPMSKH1-IFNgamma).


RESULTS
MSC showed no significant effect on circulating CTL of healthy subjects. For virus-induced CTL, MSC demonstrated approximately 50% suppression. CD8(+) cell expansion could not explain the suppressive effects of MSC. Soluble factors produced by MSC were responsible for the retention of 50% CTL responses. Cytokine microarray analyses, noncontact cultures, and functional assays identified a role for IFN-gamma. MSC were identified as the relevant source of IFN-gamma.


CONCLUSIONS
The results show a facilitating role of IFN-gamma on CTL responses, although paradoxical in light of the veto properties of MSC. This report shows that in cases where MSC are used in transplantation for repair of damaged tissue, they can exert an additional role by protecting the host to viral challenges and thereby protect from its immunosuppressive properties.
Kang
Helen S
HS
Department of Medicine, UMDNJ, Newark, NJ 07103, USA.
Habib
Misha
M
Chan
Jennifer
J
Abavana
Christina
C
Potian
Julius A
JA
Ponzio
Nicholas M
NM
Rameshwar
Pranela
P
D000293:Adolescent; D000328:Adult; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D034801:Mastocytoma; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D029082:Sendai virus / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology* / Q000821:virology*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D017931:DNA Primers; D007371:Interferon-gamma