Intravenous Infusion of Mesenchymal Stem/Stromal Cells Decreased CCR7+ Antigen Presenting Cells in Mice with Corneal Allotransplantation

Purpose: To investigate the effects of intravenous (IV) infusion of human mesenchymal stem/stromal cells (hMSCs) on activation and migration of CCR7(+) antigen presenting cells (APCs) in allogeneic corneal transplantation. Materials and Methods: We first analyzed the cellular and molecular profiles of draining lymph nodes (DLNs) in early and late phases after syngeneic or allogeneic corneal transplantation in mice, and then investigated the effects of hMSCs on APCs expressing CCR7, a key molecule implicated in APC migration to DLNs. Results: After early transplantation, the numbers of MHC class II(+)CD11b(+)CD11c(+), MHC class II(+)CD11b(-)CD11c(+), and MHC II(+)CD11b(+)CD11c(+) cells as well as the levels of APC-derived cytokines (IL-12a and IL-12b) driving the Th1 response were increased in both syngeneic and allogeneic transplants indicating activation of APCs. In late phase, the numbers of CD3(+)CD4(+)CD8(-) and CD3(+)CD4(-)CD8(+) cells and the levels of T cell-derived cytokines were increased in allogeneic transplants, but not in syngeneic transplants indicating immune rejection. The peri-transplant infusion of IV hMSCs significantly reduced the numbers of CCR7(+)CD11b(+) or CCR7(+)CD11c(+) cells in DLNs and the cornea in the early phase. Also, the expression of CCR7 and its ligands, CCL19, CCL21, and CXC3R as well as IL-12 were markedly decreased by hMSCs in the cornea and DLNs. Conclusions: IV hMSCs reduced the activation and migration of CCR7(+) APCs in the cornea and DLNs in allogeneic corneal transplantation.