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  • Title: Programmed death-1 signaling is essential for the skin allograft protection by alternatively activated dendritic cell infusion in mice.
    Author: Dai H, Zhu H, Lei P, Yagita H, Liu J, Wen X, Zhou W, Gong F, Shen G, Fang M.
    Journal: Transplantation; 2009 Oct 15; 88(7):864-73. PubMed ID: 19935456.
    Abstract:
    BACKGROUND: Alternatively activated dendritic cell (aaDC) can prolong allograft survival in the mouse model. However, the molecular mechanism(s) by which these DCs function to regulate alloreactive T-cell responses remains to be clearly defined. METHODS: Bone marrow-derived DCs were incubated in the presence of interleukin (IL)-10 (immature DC), stimulated with lipopolysaccharide only (mature DC), or pretreated with IL-10 and then activated with lipopolysaccharide (aaDC). These cells were compared for their phenotypes and regulatory capacities both in vitro and in vivo. In addition, programmed death-1 (PD-1)/PD-L pathway was blocked to test its contribution to the regulatory function of aaDC. RESULTS: The expression of surface major histocompatibility complex class II, CD80, and CD86 on aaDC was lower than that on mDC, whereas aaDC had a higher expression of PD-L1 and PD-L2 compared with immature DC or untreated DC. In vitro co-culture of aaDC with allogeneic T cells led to a significant decrease in the T-cell response as well as a reduction of interferon-gamma secretion and an enhanced IL-10 production while CD4 CD25 Foxp3 T cells were expanded. Interestingly, these regulatory effects of aaDC were partially abolished when PD-1/PD-L pathway was blocked using anti-PD-1 blocking antibody. Infusion of BALB/c donor-derived aaDC into naive C57BL/6 recipients resulted in a significantly prolonged skin allograft survival, which was, at least in part, PD-1/PD-L pathway dependent. CONCLUSION: Our data indicate that the PD-1/PD-L pathway plays an important role in aaDC-mediated prolongation of skin allograft survival.
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