Gr-1int CD11B+ 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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 languageEnglish
Pages (from-to)1453-1463
Number of pages11
JournalJournal of Leukocyte Biology
Volume100
Issue number6
DOIs
Publication statusPublished - 2016 Dec 1

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

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