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-1CD11b cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1CD11b cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1CD11b cells, but not Gr-1CD11b 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-1CD11b cells. Furthermore, adoptive transfer of Gr-1CD11b cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-γ in allograft areas is essential for development of Gr-1CD11b MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival.

Rapamycin Nano-Micelle Ophthalmic Solution Reduces Corneal Allograft Rejection by Potentiating Myeloid-Derived Suppressor Cells' Function

“…It has been reported that MDSCs are involved in the pathogenesis of corneal allograft rejection ( 25 – 27 ) and that RAPA prolongs cardiac-allograft survival and alleviates acute kidney injury by inducing MDSC recruitment and strengthening their immunosuppressive activity ( 28 , 29 ). Based on these findings, we investigated whether MDSCs are associated with the RAPA-induced anti-rejection effect in corneal-transplantation models.…”

Myeloid-derived suppressor cells expand after transplantation and their augmentation increases graft survival

“…However, MDSCs are known to expand after kidney transplantation in humans 9 . Animal studies have shown that adoptive transfer of MDSCs can prolong survival of islets, skin, as well as cardiac allografts 4,5,36‐38 ; but little more is known about the ability of MDSCs to control graft survival. Our group recently showed that anti‐thymocyte globulin affects MDSC expansion and survival, suggesting that common transplant drugs may alter the immunosuppressive capacities of MDSCs 3 .…”

“…MDSCs suppress alloreactive T cell responses and have been shown to prolong islet 4 and corneal 5 graft survival. A contribution of MDSCs in tolerance has been suggested in rodent models of cardiac, 6 kidney, 7 and skin 8 transplantation.…”

Glucocorticoids induce corneal allograft tolerance through expansion of monocytic myeloid-derived suppressor cells

“…5 In transplantation, several studies demonstrated that MDSCs play an essential role in immune tolerance induction in models of kidney, skin, or heart transplantation. 20 There are several possibilities as to how MDSCs prevent allograft rejection. 20 There are several possibilities as to how MDSCs prevent allograft rejection.…”

“…[8][9][10][16][17][18][19] Furthermore, a recent study showed that infiltration of Gr-1 int CD11b + MDSCs in corneal grafts during the early postoperative days led to acceptance of corneal allografts. 20 There are several possibilities as to how MDSCs prevent allograft rejection. One is that MDSCs suppress T cells through iNOS expression and NO production.…”