September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Gr-1intCD11b+, not Gr1+CD11b+, cells, are myeloid-derived suppressor cells(MDSCs) in murine corneal allograft and induced by high dose IFN-γ
Author Affiliations & Notes
  • Wungrak Choi
    Preventive Medicine , Yonsei University College of Medicine, Institute of Vision Research, Seoul, Korea (the Republic of)
  • Yong woo Ji
    Preventive Medicine , Yonsei University College of Medicine, Institute of Vision Research, Seoul, Korea (the Republic of)
  • Eunyoung Choi
    Preventive Medicine , Yonsei University College of Medicine, Institute of Vision Research, Seoul, Korea (the Republic of)
  • Inhee Moon
    Preventive Medicine , Yonsei University College of Medicine, Institute of Vision Research, Seoul, Korea (the Republic of)
  • Hwa-Yong Ham
    Preventive Medicine , Yonsei University College of Medicine, Institute of Vision Research, Seoul, Korea (the Republic of)
  • Areum Yeo
    Preventive Medicine , Yonsei University College of Medicine, Institute of Vision Research, Seoul, Korea (the Republic of)
  • Hyemi Noh
    Preventive Medicine , Yonsei University College of Medicine, Institute of Vision Research, Seoul, Korea (the Republic of)
  • Jong Suk Song
    Department of Ophthalmology, Korea University College of Medicine, Seoul, Korea, Seoul, Korea (the Republic of)
  • Hyeon Chang Kim
    Preventive Medicine , Yonsei University College of Medicine, Institute of Vision Research, Seoul, Korea (the Republic of)
  • Eung Kweon Kim
    Preventive Medicine , Yonsei University College of Medicine, Institute of Vision Research, Seoul, Korea (the Republic of)
    Ophthalmology, Yonsei University College of Medicine, Institute of Corneal Dystrophy Research, Seoul, Korea (the Republic of)
  • Hyung Keun Lee
    Preventive Medicine , Yonsei University College of Medicine, Institute of Vision Research, Seoul, Korea (the Republic of)
    Ophthalmology, Yonsei University College of Medicine, Institute of Corneal Dystrophy Research, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Wungrak Choi, None; Yong woo Ji, None; Eunyoung Choi, None; Inhee Moon, None; Hwa-Yong Ham, None; Areum Yeo, None; Hyemi Noh, None; Jong Suk Song, None; Hyeon Chang Kim, None; Eung Kweon Kim, None; Hyung Keun Lee, None
  • Footnotes
    Support  This work was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Korea. (HI13C0055).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1433. doi:
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      Wungrak Choi, Yong woo Ji, Eunyoung Choi, Inhee Moon, Hwa-Yong Ham, Areum Yeo, Hyemi Noh, Jong Suk Song, Hyeon Chang Kim, Eung Kweon Kim, Hyung Keun Lee; Gr-1intCD11b+, not Gr1+CD11b+, cells, are myeloid-derived suppressor cells(MDSCs) in murine corneal allograft and induced by high dose IFN-γ. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1433.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Although corneal allotransplantation is performed in the immune-privileged cornea,many grafts are still rejected after transplantation.The purpose of this study was to examine the characteristics of myeloid-derived immunosuppressive cells(MDSCs) and investigate their mechanism of induction and functional role in corneal allotransplantation using murine corneal allograft model.

Methods : C57BL/6 mice cornea was used for donor and was sutured onto recipient graft beds in central cornea of BALB/c, resulting in an allogeneic graft. Microscopic evaluation was done weekly for 8 weeks.To generate in-vitro MDSCs, mouse femur BM cells were treated with granulocyte macrophage-colony stimulating factor (GM-CSF) and different cytokines as transforming growth factor(TGF)-β, interleukin(IL)-10, IL-13, and interferon(IFN)-γ with different concentrations ranging from 10 ng to 10 μg.Gr-1 and CD11b double expressing cells were defined as mouse MDSCs.

Results : Gr-1+CD11b+ MDSCs were infiltrated to allografted area in murine corneal allograft model from the early phase of allograft.Distribution of Gr-1+CD11b+ cells were equal between accepted and rejected corneas, peripheral blood and bone marrow.However the ratio of Gr-1intCD11b+/Gr-1+CD11b+ cells were higher in accepted corneal grafts compared to rejected grafts(p<0.001).Gr-1intCD11b+ cells were found to dominantly infiltrate into the accepted corneal graft and expressed high levels of immunosuppressive cytokines,including TGF-β, IL-10, and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL).We found that high dose, not low dose, of IFN-γ and GM-CSF could induce immunosuppressive cytokine expressing Gr-1intCD11b+ cells with in vitro cell culture.Also, Gr1intCD11b+ cells, generated by high dose IFN-γ and GM-CSF in vitro were injected to the peripheral blood and were confirmed to infiltrate into peri-graft area and reduce graft rejection.

Conclusions : Gr-1intCD11b+, not Gr1+CD11b+, cells can be MDSCs in murine corneal allograft model and secrete immune suppressive molecules like IL-10, TGF-β, and TRAIL which, results in improvement of allograft survival.With the in vitro condition, high-dose IFN-γ in allograft area is needed for development of Gr-1intCD11b+ MDSCs.This may indicate that certain cytokine milieu changes during the early period of allografts may result in differences of graft survival and rejection.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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