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Hwa Yong Ham, Wungrak Choi, Hyemi Noh, Areum Yeo, Insil Song, Jihwan Min, Hyung Keun Lee; Myeloid Derived Suppressor Cells (MDSCs) Induce Tolergenic Dendritic Cells in Corneal Allograft Model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4026.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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-1high and Gr-1INT cells. Interestingly, the frequency of Gr-1INTCD11b+ cells were higher in graft acceptor than in rejected cornea. Additionally, the MHC class II expressing population were not different between Gr-1INTCD11b+ and of Gr-1highCD11b+. However, the expression of CD86 and CD80 was significantly reduced in Gr-1INTCD11b+ cells from accepted grafts. Lastly, Gr-1INTCD11b+ cells were found as reduced naive T cell activation and proliferation from co-culture assay.
Gr-1INTCD11b+ cells, not Gr-1highCD11b+ 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.
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