PMID- 18178870 OWN - NLM STAT- MEDLINE DCOM- 20080415 LR - 20210206 IS - 0006-4971 (Print) IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 111 IP - 5 DP - 2008 Mar 1 TI - Organ-derived dendritic cells have differential effects on alloreactive T cells. PG - 2929-40 LID - 10.1182/blood-2007-06-096602 [doi] AB - 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. FAU - Kim, Theo D AU - Kim TD AD - Department of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. FAU - Terwey, Theis H AU - Terwey TH FAU - Zakrzewski, Johannes L AU - Zakrzewski JL FAU - Suh, David AU - Suh D FAU - Kochman, Adam A AU - Kochman AA FAU - Chen, Megan E AU - Chen ME FAU - King, Chris G AU - King CG FAU - Borsotti, Chiara AU - Borsotti C FAU - Grubin, Jeremy AU - Grubin J FAU - Smith, Odette M AU - Smith OM FAU - Heller, Glenn AU - Heller G FAU - Liu, Chen AU - Liu C FAU - Murphy, George F AU - Murphy GF FAU - Alpdogan, Onder AU - Alpdogan O FAU - van den Brink, Marcel R M AU - van den Brink MR LA - eng GR - P20 CA 103694/CA/NCI NIH HHS/United States GR - CA 107096/CA/NCI NIH HHS/United States GR - R01 HL069929/HL/NHLBI NIH HHS/United States GR - R01 CA107096/CA/NCI NIH HHS/United States GR - P01 CA023766/CA/NCI NIH HHS/United States GR - CA 33049/CA/NCI NIH HHS/United States GR - P01 CA033049/CA/NCI NIH HHS/United States GR - P30 AR042689/AR/NIAMS NIH HHS/United States GR - P30 CA008748/CA/NCI NIH HHS/United States GR - CA 023766/CA/NCI NIH HHS/United States GR - R01 HL084815/HL/NHLBI NIH HHS/United States GR - P30 AR042689-159006/AR/NIAMS NIH HHS/United States GR - P20 CA103694/CA/NCI NIH HHS/United States GR - R01 HL084815-17/HL/NHLBI NIH HHS/United States GR - HL 69929/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080104 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Integrins) RN - 0 (Isoantigens) RN - 0 (Ligands) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, Lymphocyte Homing) RN - 0 (Selectins) RN - 0 (integrin alpha4beta7) SB - IM MH - Animals MH - Cell Proliferation/drug effects MH - Dendritic Cells/*cytology/drug effects/*immunology MH - Gene Expression Profiling MH - Graft vs Host Disease MH - Humans MH - Integrins/metabolism MH - Isoantigens/*immunology MH - Ligands MH - Lipopolysaccharides/pharmacology MH - Liver/cytology/drug effects MH - Lymphocyte Activation/drug effects MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Oligonucleotide Array Sequence Analysis MH - Organ Specificity/drug effects MH - Phenotype MH - Receptors, Lymphocyte Homing/genetics/metabolism MH - Selectins/metabolism MH - Survival Rate MH - T-Lymphocytes/cytology/drug effects/*immunology MH - Up-Regulation/drug effects/genetics PMC - PMC2254543 EDAT- 2008/01/08 09:00 MHDA- 2008/04/16 09:00 PMCR- 2009/03/01 CRDT- 2008/01/08 09:00 PHST- 2008/01/08 09:00 [pubmed] PHST- 2008/04/16 09:00 [medline] PHST- 2008/01/08 09:00 [entrez] PHST- 2009/03/01 00:00 [pmc-release] AID - S0006-4971(20)51576-0 [pii] AID - 2007/096602 [pii] AID - 10.1182/blood-2007-06-096602 [doi] PST - ppublish SO - Blood. 2008 Mar 1;111(5):2929-40. doi: 10.1182/blood-2007-06-096602. Epub 2008 Jan 4.