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목적 : We previously demonstrated that peritransplant intravenous (IV) infusion of human MSCs (hMSCs) prolonged the survival of allogeneic corneal transplants in mice, and suppressed early surgery-induced inflammation in the cornea [6]. To further explore the mechanism of MSCs in promoting the survival of corneal allotransplants, we here tested a hypothesis that a decrease in early corneal inflammation by hMSCs might lead to a decrease in migration and activation of antigen presenting cells (APCs) in draining lymph nodes (DLNs), and subsequently immune rejection might be prevented.
방법 : We first analyzed cellular and molecular profiles of DLNs in early and late phases after syngeneic or allogeneic corneal transplantation, and then investigated the effects of hMSCs on the profiles of DLNs.
결과 : In early phase , the numbers of MHC class II+CD11b+CD11c-, MHC class II+CD11b-CD11c+, and MHC II+CD11b+CD11c+ cells were increased in both syngeneic and allogeneic transplants, and were reduced by IV hMSCs. Especially, hMSCs reduced the numbers of CD11b+ or CD11c+ cells expressing CCR7. Also, the expression of CCR7, CCL21, CXC3R, and IL-12 were decreased by hMSCs. In late phase, the numbers of CD3+CD4+CD8- and CD3+CD4-CD8+ cells were increased in allogeneic transplants, indicating immune rejection. The hMSCs decreased CD4+ or CD8+ T cells and expression of IL-2, IFN-γ, granzymes A and B.
결론 : Given that hMSCs rapidly disappear from the system after IV infusion, data suggested that peritransplant IV hMSCs reduced the activation and migration of antigen presenting cells in DLNs in early phase, and subsequently prevented immune rejection by inhibiting an afferent limb of immune responses.
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