Abstract
We identified the characteristics of myeloid-derived suppressor cells (MDSCs) and investigated their mechanism of induction and their functional role in allograft rejection using a murine corneal allograft model. In mice, MDSCs coexpress CD11b and myeloid differentiation antigen Gr-1. Gr-1+CD11b+cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1+CD11b+cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1intCD11b+cells, but not Gr-1hiCD11b+cells, infiltrated the accepted graft early after surgery and expressed high levels of immunosuppressive cytokines, including IL-10, TGF-β, and TNF-related apoptosis-inducing ligand. This population remained until 4 wk after surgery. In vitro, only high dose (>100 ng/ml) of IFN-γ plus GM-CSF could induce immunosuppressive cytokine expression in Gr-1intCD11b+ cells. Furthermore, adoptive transfer of Gr-1intCD11b+cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-γ in allograft areas is essential for development of Gr-1intCD11b+ MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival.
| Original language | English |
|---|---|
| Pages (from-to) | 1453-1463 |
| Number of pages | 11 |
| Journal | Journal of Leukocyte Biology |
| Volume | 100 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2016 Dec 1 |
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Keywords
- Adoptive transfer
- Interferon-γ (IFN-γ)
- Keratoplasty
- Myeloid differentiation antigen Gr-1
- TNF-related apoptosis-inducing ligand (TRAIL)
ASJC Scopus subject areas
- Immunology
- Cell Biology
Cite this
Gr-1int CD11B+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival. / Choi, Wungrak; Ji, Yong Woo; Ham, Hwa Yong; Yeo, Areum; Noh, Hyemi; Jin, Su Eon; Song, Jong-Suk; Kim, Hyeon Chang; Kim, Eung Kwon; Lee, Hyung Keun.
In: Journal of Leukocyte Biology, Vol. 100, No. 6, 01.12.2016, p. 1453-1463.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Gr-1int CD11B+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival
AU - Choi, Wungrak
AU - Ji, Yong Woo
AU - Ham, Hwa Yong
AU - Yeo, Areum
AU - Noh, Hyemi
AU - Jin, Su Eon
AU - Song, Jong-Suk
AU - Kim, Hyeon Chang
AU - Kim, Eung Kwon
AU - Lee, Hyung Keun
PY - 2016/12/1
Y1 - 2016/12/1
N2 - We identified the characteristics of myeloid-derived suppressor cells (MDSCs) and investigated their mechanism of induction and their functional role in allograft rejection using a murine corneal allograft model. In mice, MDSCs coexpress CD11b and myeloid differentiation antigen Gr-1. Gr-1+CD11b+cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1+CD11b+cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1intCD11b+cells, but not Gr-1hiCD11b+cells, infiltrated the accepted graft early after surgery and expressed high levels of immunosuppressive cytokines, including IL-10, TGF-β, and TNF-related apoptosis-inducing ligand. This population remained until 4 wk after surgery. In vitro, only high dose (>100 ng/ml) of IFN-γ plus GM-CSF could induce immunosuppressive cytokine expression in Gr-1intCD11b+ cells. Furthermore, adoptive transfer of Gr-1intCD11b+cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-γ in allograft areas is essential for development of Gr-1intCD11b+ MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival.
AB - We identified the characteristics of myeloid-derived suppressor cells (MDSCs) and investigated their mechanism of induction and their functional role in allograft rejection using a murine corneal allograft model. In mice, MDSCs coexpress CD11b and myeloid differentiation antigen Gr-1. Gr-1+CD11b+cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1+CD11b+cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1intCD11b+cells, but not Gr-1hiCD11b+cells, infiltrated the accepted graft early after surgery and expressed high levels of immunosuppressive cytokines, including IL-10, TGF-β, and TNF-related apoptosis-inducing ligand. This population remained until 4 wk after surgery. In vitro, only high dose (>100 ng/ml) of IFN-γ plus GM-CSF could induce immunosuppressive cytokine expression in Gr-1intCD11b+ cells. Furthermore, adoptive transfer of Gr-1intCD11b+cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-γ in allograft areas is essential for development of Gr-1intCD11b+ MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival.
KW - Adoptive transfer
KW - Interferon-γ (IFN-γ)
KW - Keratoplasty
KW - Myeloid differentiation antigen Gr-1
KW - TNF-related apoptosis-inducing ligand (TRAIL)
UR - http://www.scopus.com/inward/record.url?scp=85003015154&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85003015154&partnerID=8YFLogxK
U2 - 10.1189/jlb.5A1115-508RR
DO - 10.1189/jlb.5A1115-508RR
M3 - Article
VL - 100
SP - 1453
EP - 1463
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 6
ER -