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)
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U2 - 10.1189/jlb.5A1115-508RR
DO - 10.1189/jlb.5A1115-508RR
M3 - Article
C2 - 27370015
AN - SCOPUS:85003015154
VL - 100
SP - 1453
EP - 1463
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 6
ER -