Although both embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) are known to have immunosuppressive effects, the mechanisms of immunosuppression are still controversial. Both types of stem cells suppressed not only the proliferation but also survival of CD4+ T cells in vitro. They suppressed secretion of various cytokines (IL-2, IL-12, IFN-γ, TNF-α, IL-4, IL-5, IL-1β, and IL-10), whereas there was no change in the levels of TGF-β or IDO. Classic and modified transwell experiments demonstrated that immunosuppressive activities were mainly mediated by cell-to-cell contact. Granzyme B in the ESCs played a significant role in their immunosuppression, whereas PDL-1, Fas ligand, CD30 or perforin was not involved in the contact-dependent immunosuppression. However, none of the above molecules played a significant role in the immunosuppression by the MSCs. Interestingly, both stem cells increased the proportion of Foxp3+ regulatory T cells. Our results showed that both ESCs and MSCs suppressed the survival as well as the proliferation of T cells by mainly contact-dependent mechanisms and increased the proportion of regulatory T cells. Granzyme B was involved in immunosuppression by the ESCs in a perforin-independent manner.
Bibliographical noteFunding Information:
We thank Su-Kil Seo (University of INJE College of Medicine, Pusan, Korea) for measuring IDO activity. This work was supported by both the Korea Research Foundation Grant funded by the Korean government (MOEHRD, Basic Research Promotion Fund, KRF-2009-0074949 ), and a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (project no. A084760).
- Embryonic stem cells
- Granzyme B
- Mesenchymal stem cells
ASJC Scopus subject areas
- Immunology and Allergy