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Suppression of cellular immunity by cord blood-derived unrestricted somatic stem cells is cytokine-dependent

Lookup NU author(s): Dr Xiao WangORCiD, Dr Michelle Rae, Professor Anne Dickinson

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Abstract

Unrestricted somatic stem cells (USSC) have the potential to differentiate into tissues derived from all three germinal layers and therefore hold promise for use in regenerative therapies. Furthermore, they have haematopoietic stromal activity, a characteristic that may be exploited to enhance haematopoietic engraftment. Both applications may require USSC to be used in an allogeneic, HLA-mismatched setting. We have therefore studied their in vitro interaction with cellular immunity. USSC showed no allostimulatory activity and caused only minimal inhibition of allogeneic T-cell responses. However, following pre-stimulation with IFN gamma and TNF alpha, they inhibited T-cell proliferation in an indoleamine 2, 3-dioxygenase-dependent manner and suppressed graft-versus-host type reactions. In addition, USSC inhibited DC maturation and function. This inhibition was overridden by stronger DC maturation signals provided by IL-1 beta, IL-6, PGE(2) and TNF alpha compared to TNF alpha alone. Pre-stimulation of USSC with IFN gamma and TNF alpha had a similar effect: Inhibition of DC maturation was no longer observed. Thus, USSC are conditionally immunosuppressive, and IFN gamma and TNF alpha constitute a switch, which regulates their immunological properties. They either suppress T-cell responses in the presence of both cytokines or in their absence block DC differentiation and function. These activities may contribute to fine-tuning the immune system especially at sites of tissue damage in order to ensure appropriate differentiation of USSC and subsequent tissue repair. Therapeutically, they may help to protect USSC and possibly their progeny from immune rejection.

Publication metadata

Author(s): Winter M, Wang XN, Daubener W, Eyking A, Rae M, Dickinson AM, Wernet P, Kogler G, Sorg RV

Publication type: Article

Publication status: Published

Journal: Journal of Cellular and Molecular Medicine

Year: 2009

Volume: 13

Issue: 8B

Pages: 2465-2475

ISSN (print): 1582-1838

ISSN (electronic): 1582-4934

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/j.1582-4934.2008.00566.x

DOI: 10.1111/j.1582-4934.2008.00566.x

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