Organ-derived dendritic cells have differential effects on alloreactive T cells

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Abstract

Dendritic cells (DCs) are considered critical for the induction of graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In addition to their priming function, dendritic cells have been shown to induce organ-tropism through induction of specific homing molecules on T cells. Using adoptive transfer of CFSE-labeled cells, we first demonstrated that alloreactive T cells differentially up- regulate specific homing molecules in vivo. Host-type dendritic cells from the GVHD target organs liver and spleen or skin-and gut-draining lymph nodes effectively primed naive allogeneic T cells in vitro with the exception of liver-derived dendritic cells, which showed less stimulatory capacity. Gut-derived dendritic cells induced alloreactive donor T cells with a gut-homing phenotype that caused increased GVHD mortality and morbidity compared with T cells stimulated with dendritic cells from spleen, liver, and peripheral lymph nodes in an MHC-mismatched murine BMT model. However, in vivo analysis demonstrated that the in vitro imprinting of homing molecules on alloreactive T cells was only transient. In conclusion, organ-derived dendritic cells can efficiently induce specific homing molecules on alloreactive T cells. A gut-homing phenotype correlates with increased GVHD mortality and morbidity after murine BMT, underlining the importance of the gut in the pathophysiology of GVHD. © 2008 by The American Society of Hematology.

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Kim, T. D., Terwey, T. H., Zakrzewski, J. L., Suh, D., Kochman, A. A., Chen, M. E., … Van Den Brink, M. R. M. (2008). Organ-derived dendritic cells have differential effects on alloreactive T cells. Blood, 111(5), 2929–2940. https://doi.org/10.1182/blood-2007-06-096602

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