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• W2170199596 abstract "Little is known about heart tissue/donor dendritic cells, which play a key role in mounting alloimmune responses. In this report, we focus on three primary features of donor dendritic cells: their generation, their trafficking after transplantation, and their role in regulating tolerance <i>versus</i> rejection. Using transgenic mice as donors of heart allografts enabled us to monitor trafficking of donor dendritic cells after transplantation. Donor dendritic cells rapidly migrated into secondary lymphoid tissues within 3 h of transplantation. We found that the chemokine receptor CX3CR1 regulates the generation of heart tissue dendritic cells constitutively. Compared with wild-type hearts, CX3CR1^−/− hearts contained fewer dendritic cells, and heart allografts from CX3CR1^−/− donors survived significantly longer without immunosuppression. Unexpectedly, though, co-stimulatory blockade with anti-CD154 or CTLA4-Ig induced long-term survival for wild-type heart allografts but not for CX3CR1^−/− heart allografts. Increasing the dendritic cell frequency in CX3CR1^−/− hearts by treatment with Flt3L restored the anti-CD154–induced prolongation of CX3CR1^−/− heart allograft survival. Compared with wild-type donors, depleting transgenic donors of dendritic cells before heart transplantation also markedly worsened chronic rejection under anti-CD154 treatment. These data indicate the importance of the CX3CR1 pathway in the generation of heart tissue dendritic cells and the divergent role of tissue/dendritic cells in rejection <i>versus</i> tolerance." @default.
• W2170199596 created "2016-06-24" @default.
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• W2170199596 date "2009-03-01" @default.
• W2170199596 modified "2023-09-25" @default.
• W2170199596 title "Divergent Role of Donor Dendritic Cells in Rejection versus Tolerance of Allografts" @default.
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• W2170199596 doi "https://doi.org/10.1681/asn.2008040377" @default.
• W2170199596 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2653678" @default.
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