title: Gr-1intCD11b+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival.
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.
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Wungrak
authors.initials: W
authors.lastname: Choi
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.|Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Ji
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hwa-Yong
authors.initials: HY
authors.lastname: Ham
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Yeo
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyemi
authors.initials: H
authors.lastname: Noh
authors.affiliation: College of Pharmacy, Yonsei University, Incheon, Korea.
authors.forename: Su-Eon
authors.initials: SE
authors.lastname: Jin
authors.affiliation: Department of Ophthalmology, Korea University College of Medicine, Seoul, Korea.
authors.forename: Jong Suk
authors.initials: JS
authors.lastname: Song
authors.affiliation: Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyeon Chang
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.|Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eung Kwon
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea; shadik@yuhs.ac.|Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyung Keun
authors.initials: HK
authors.lastname: Lee
mesh_terms: D019264:Adoptive Transfer; D064591:Allografts / Q000276:immunology; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D017209:Apoptosis; D039481:CD11b Antigen / Q000032:analysis; D016039:Corneal Transplantation; D016207:Cytokines / Q000096:biosynthesis; D006082:Graft Enhancement, Immunologic / Q000379:methods*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000072737:Myeloid-Derived Suppressor Cells / Q000145:classification / Q000276:immunology* / Q000637:transplantation; D011828:Radiation Chimera
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; D016207:Cytokines; C480309:Ly6G antigen, mouse; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: TNF-related apoptosis-inducing ligand (TRAIL); adoptive transfer; interferon-γ (IFN-γ); keratoplasty; myeloid differentiation antigen Gr-1