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Gr-1intCD11b+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival

 Wungrak Choi  ;  Yong Woo Ji  ;  Hwa-Yong Ham  ;  Areum Yeo  ;  Hyemi Noh  ;  Su-Eon Jin  ;  Jong Suk Song  ;  Hyeon Chang Kim  ;  Eung Kwon Kim  ;  Hyung Keun Lee 
 Journal of Leukocyte Biology, Vol.100(6) : 1453-1463, 2016 
Journal Title
 Journal of Leukocyte Biology 
Issue Date
Adoptive Transfer ; Allografts/immunology ; Animals ; Antigens, Ly/analysis ; Apoptosis ; CD11b Antigen/analysis ; Corneal Transplantation* ; Cytokines/biosynthesis ; Graft Enhancement, Immunologic/methods* ; Graft Rejection/immunology ; Graft Survival ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Immunophenotyping ; Interferon-gamma/pharmacology ; Lymphocyte Subsets/cytology ; Lymphocyte Subsets/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells/classification ; Myeloid-Derived Suppressor Cells/immunology* ; Myeloid-Derived Suppressor Cells/transplantation ; Radiation Chimera
TNF-related apoptosis-inducing ligand (TRAIL) ; adoptive transfer ; interferon-γ (IFN-γ) ; keratoplasty ; myeloid differentiation antigen Gr-1
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.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine and Public Health (예방의학교실) > 1. Journal Papers
Yonsei Authors
김응권(Kim, Eung Kweon) ORCID logo https://orcid.org/0000-0002-1453-8042
김현창(Kim, Hyeon Chang) ORCID logo https://orcid.org/0000-0001-7867-1240
이형근(Lee, Hyung Keun) ORCID logo https://orcid.org/0000-0002-1123-2136
지용우(Ji, Yong Woo)
최웅락(Choi, Wungrak) ORCID logo https://orcid.org/0000-0002-3015-2502
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