@article {1213826, title = {Corneal Tissue From Dry Eye Donors Leads to Enhanced Graft Rejection}, journal = {Cornea}, volume = {37}, number = {1}, year = {2018}, month = {2018 Jan}, pages = {95-101}, abstract = {PURPOSE: To assess the effect of dry eye disease (DED) in graft donors on dendritic cell (DC) maturation, host T-cell sensitization, and corneal allograft rejection. METHODS: Corneas of control (healthy donor) and DED mice (C57BL/6) were transplanted onto fully allogeneic naive BALB/c recipients (n = 10 mice/group). Long-term allograft survival was evaluated for 8 weeks. Corneas and draining lymph nodes (dLNs) were harvested at posttransplantation day 14 (n = 5 mice/group). The frequencies of MHCII CD11c DCs in the donor corneas and host dLNs and the frequencies of interferon (IFN)-γ and IL-17 CD4 T cells and Foxp3 expression by Tregs in host dLNs were investigated using flow cytometry. The enzyme-linked immunospot assay was used to assess host T-cell allosensitization through direct and indirect pathways (n = 3/group). RESULTS: Recipients of DED donor corneas showed significantly reduced graft survival (10\%) compared with control mice (50\% survival, P = 0.022), and had significantly increased frequencies of mature DCs in the grafted cornea (DED donor 44.0\% {\textpm} 0.36\% vs. healthy donor 35.4 {\textpm} 0.5\%; P \< 0.0001) and host dLNs (DED donor 25.1\% {\textpm} 0.66\% vs. healthy donor 13.7\% {\textpm} 1.6\%; P = 0.005). Frequencies of IFN-γ and IL-17 T cells were increased in the dLNs of recipients of DED corneas, whereas the expression (mean fluorescence intensity) of Foxp3 in Tregs was decreased significantly in these mice (DED donor 6004 {\textpm} 193 vs. healthy donor 6806 {\textpm} 81; P = 0.0002). Enzyme-linked immunospot analysis showed that the direct pathway of allosensitization was significantly amplified in recipients of grafts with DED (P = 0.0146). CONCLUSIONS: Our results indicate that DED in the donor is a significant risk factor for subsequent corneal allograft rejection.}, issn = {1536-4798}, doi = {10.1097/ICO.0000000000001400}, author = {Inomata, Takenori and Hua, Jing and Nakao, Takeshi and Shiang, Tina and Chiang, Homer and Amouzegar, Afsaneh and Dana, Reza} }