Myeloid Derived Suppressor Cells (MDSCs) Induce Tolergenic Dendritic Cells in Corneal Allograft Model

Abstract

Purpose: Myeloid derived suppressor cells (MDSCs) comprise heterogenous population cells that suppress the immune response. Dendritic cells (DCs) are well-established antigen presenting cell (APC) which play critical role in immune tolerance. We aimed to determined the role of MDSC like as tolergenic DC in corneal allograft mouse model.

Methods: In this study, orthotic penetrating keratoplasty was performed to six-week-old male C57BL/6 and BALB/c mice. Graft survival and vascular ingrowth were investigated until 4 weeks after surgery. At 1, 2, and 4 weeks after surgery, mononuclear cells in bone marrow, peripheral blood, lymph node, and cornea were collected and surface markers for Gr-1, CD11b, major histocompatibility complex (MHC)-II, co-stimulatory molecules (CD80, CD86) and cytokine levels were measured.

Results: Gr-1⁺CD11b⁺ cells were found to be infiltrated in dornor cornea and recipient LNs from 2nd day after surgery. With the expression level of Gr-1 marker, Gr-1⁺CD11b⁺ cells were subdivided by Gr-1^high and Gr-1^INT cells. Interestingly, the frequency of Gr-1^INTCD11b⁺ cells were higher in graft acceptor than in rejected cornea. Additionally, the MHC class II expressing population were not different between Gr-1^INTCD11b⁺ and of Gr-1^highCD11b⁺. However, the expression of CD86 and CD80 was significantly reduced in Gr-1^INTCD11b⁺ cells from accepted grafts. Lastly, Gr-1^INTCD11b⁺ cells were found as reduced naive T cell activation and proliferation from co-culture assay.

Conclusions: Gr-1^INTCD11b⁺ cells, not Gr-1^highCD11b⁺ cells, were found as MDSC and may be able to play as tolergenic DC in allogenic accepted group. These cells induce T cell anergy response and immune tolerance in corneal allograft mouse model.