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.
Bibliographical noteFunding Information:
This work was supported by Advanced Science Research Program (Grant NRF-2015R1A2A2A04002684) through the National Research Foundation of Korea and was partially supported by a grant of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (HI13C0055). The authors thank Daniel R. Saban, PhD, Duke University School of Medicine, Durham, NC, USA, and Lark Kyun Kim, PhD, Yonsei University School of Medicine, Severance Biomedical Science Institute, Seoul, Korea, for excellent discussion that assisted in data analysis.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Cell Biology