Journal
TRANSPLANT IMMUNOLOGY
Volume 18, Issue 3, Pages 208-219Publisher
ELSEVIER
DOI: 10.1016/j.trim.2007.08.006
Keywords
transplantation; dendritic cells; immune tolerance; indoleamine 2,3 dioxygenase; regulatory T cells; allograft
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Despite recent extensive studies, the molecular mechanism through which DCs induce allograft tolerance largely remains poorly understood. In the current study, we presented strong evidence supporting a role for IDO in DC-mediated allograft tolerance. Pre-treatment of recipient mice with IDO-transduced donor-specific BMDCs induced skin allograft tolerance in an antigen-dependent manner. Our data suggest that IDO-expressing DCs may regulate a delicate balance of cytokines that favors the differentiation of naive CD4(+) T cells into Tregs instead of CD4+ effector T cells. In addition, BMDCs with forced IDO expression also have higher capability to expand natural Tregs. In consistent with the observation of augmented Tregs detected in the recipient mice, the capacity for splenic T cell alloresponse was significantly reduced in recipient mice pre-treated with IDO-transduced BMDCs. Furthermore, the expression of inflammatory cytokines such as IL-2, IFN gamma, IL-6, IL-17A and IL-23p19, in splenic T cells of these recipient mice, was significantly lower as compared to that of recipient mice pre-treated with either GFP-transduced BMDCs or untransduced BMDCs. (c) 2007 Elsevier B.V All tights reserved.
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