Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 7-15 |
| Number of pages | 9 |
| Journal | Transplant Immunology |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2011 Jul 1 |
| Externally published | Yes |
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Keywords
- Embryonic stem cells
- Granzyme B
- Immunosuppression
- Mesenchymal stem cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Transplantation
Cite this
Immunosuppressive mechanisms of embryonic stem cells and mesenchymal stem cells in alloimmune response. / Han, Kyu Hyun; Ro, Han; Hong, Ju Ho; Lee, Eun Mi; Cho, Bumrae; Yeom, Hye Jung; Kim, Myung-Gyu; Oh, Kook Hwan; Ahn, Curie; Yang, Jaeseok.
In: Transplant Immunology, Vol. 25, No. 1, 01.07.2011, p. 7-15.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunosuppressive mechanisms of embryonic stem cells and mesenchymal stem cells in alloimmune response
AU - Han, Kyu Hyun
AU - Ro, Han
AU - Hong, Ju Ho
AU - Lee, Eun Mi
AU - Cho, Bumrae
AU - Yeom, Hye Jung
AU - Kim, Myung-Gyu
AU - Oh, Kook Hwan
AU - Ahn, Curie
AU - Yang, Jaeseok
PY - 2011/7/1
Y1 - 2011/7/1
N2 - 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.
AB - 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.
KW - Embryonic stem cells
KW - Granzyme B
KW - Immunosuppression
KW - Mesenchymal stem cells
UR - http://www.scopus.com/inward/record.url?scp=79959644782&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959644782&partnerID=8YFLogxK
U2 - 10.1016/j.trim.2011.05.004
DO - 10.1016/j.trim.2011.05.004
M3 - Article
VL - 25
SP - 7
EP - 15
JO - Transplant Immunology
JF - Transplant Immunology
SN - 0966-3274
IS - 1
ER -