Open AccessSuppression of cellular immunity by cord blood‐derived unrestricted somatic stem cells is cytokine‐dependent
Author(s) -
Winter Meike,
Wang Xiaog,
Däubener Walter,
Eyking Annette,
Rae Michelle,
Dickinson Anne M.,
Wernet Peter,
Kögler Gesine,
Sorg Rüdiger V.
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00566.x
Subject(s) - somatic cell , stem cell , cord blood , cytokine , immunity , biology , immunology , cellular immunity , microbiology and biotechnology , immune system , genetics , gene
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 IFNγ and TNFα, 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‐1β, IL‐6, PGE 2 and TNFα compared to TNFα alone. Pre‐stimulation of USSC with IFNγ and TNFα had a similar effect: Inhibition of DC maturation was no longer observed. Thus, USSC are conditionally immunosuppressive, and IFNγ and TNFα 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.