Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma.

Abstract:

:Mesenchymal stem cells (MSCs) are mostly found around the vasculature system of the adult bone marrow (BM). They function as immune suppressors, express MHC-II, are phagocytic, and support T-cell cytotoxicity. We hypothesize that these contradictory properties of MSCs are important for BM homeostasis and occur partly through antigen presentation (antigen-presenting cells [APCs]) within a narrow window. Indeed, we have verified APC functions of MSCs to recall antigens, Candida albicans and Tetanus toxoid. The target cells have been identified to be CD4(+) T cells. APC assays with IFNgamma-knockdown MSCs and with anti-IFNgamma receptor confirmed that MHC-II expression requires autocrine stimulation by IFNgamma. During APC functions, as IFNgamma levels become elevated, there was a concomitant decrease in MHC-II on MSCs. This observation was correlated with flow cytometry studies showing a gradual decrease in MHC-II expression as IFNgamma levels were increased. The reduced levels of MHC-II correlated with losses in their allogeneic potential, as indicated in mixed lymphocyte reaction. In summary, endogenous and low levels of IFNgamma are required for MHC-II expression on MSCs, and for APC functions. APC functions occur during a narrow window before IFNgamma levels are increased. The study has implications for BM protection against infection and exacerbated inflammatory responses.

journal_name

Blood

journal_title

Blood

authors

Chan JL,Tang KC,Patel AP,Bonilla LM,Pierobon N,Ponzio NM,Rameshwar P

doi

10.1182/blood-2006-01-0057

subject

Has Abstract

pub_date

2006-06-15 00:00:00

pages

4817-24

issue

12

eissn

0006-4971

issn

1528-0020

pii

2006-01-0057

journal_volume

107

pub_type

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