title: Organ-derived dendritic cells have differential effects on alloreactive T cells.
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.
authors.affiliation: Department of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Theo D
authors.initials: TD
authors.lastname: Kim
authors.forename: Theis H
authors.initials: TH
authors.lastname: Terwey
authors.forename: Johannes L
authors.initials: JL
authors.lastname: Zakrzewski
authors.forename: David
authors.initials: D
authors.lastname: Suh
authors.forename: Adam A
authors.initials: AA
authors.lastname: Kochman
authors.forename: Megan E
authors.initials: ME
authors.lastname: Chen
authors.forename: Chris G
authors.initials: CG
authors.lastname: King
authors.forename: Chiara
authors.initials: C
authors.lastname: Borsotti
authors.forename: Jeremy
authors.initials: J
authors.lastname: Grubin
authors.forename: Odette M
authors.initials: OM
authors.lastname: Smith
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
authors.forename: Onder
authors.initials: O
authors.lastname: Alpdogan
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D020869:Gene Expression Profiling; D006086:Graft vs Host Disease; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000187:drug effects; D010641:Phenotype; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D016023:Integrins; D007519:Isoantigens; D008024:Ligands; D008070:Lipopolysaccharides; D016201:Receptors, Lymphocyte Homing; D019087:Selectins; C071777:integrin alpha4beta7