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

Authors: Kim, T. D.; Terwey, T. H.; Zakrzewski, J. L.; Suh, D.; Kochman, A. A.; Chen, M. E.; King, C. G.; Borsotti, C.; Grubin, J.; Smith, O. M.; Heller, G.; Liu, C.; Murphy, G. F.; Alpdogan, O.; van den Brink, M. R. M.
Article 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. © 2008 by The American Society of Hematology.
Keywords: controlled study; survival rate; unclassified drug; genetics; mortality; nonhuman; cell proliferation; t lymphocyte; t-lymphocytes; animal cell; mouse; phenotype; animal; cytology; metabolism; animals; mice; animal tissue; gene expression profiling; spleen; dendritic cell; morbidity; animal experiment; animal model; drug effect; mice, inbred balb c; mice, inbred c57bl; c57bl mouse; skin; liver; immunology; lymphocyte activation; dendritic cells; bagg albino mouse; oligonucleotide array sequence analysis; ligand; organ specificity; graft versus host reaction; ligands; adoptive transfer; antibody specificity; lipopolysaccharide; upregulation; dna microarray; up-regulation; major histocompatibility complex; bone marrow transplantation; graft vs host disease; alloantigen; isoantigens; integrin; integrins; alloimmunity; homing receptor; integrin alpha4beta7; lipopolysaccharides; histoincompatibility; intestine lymph; selectin; receptors, lymphocyte homing; selectins
Journal Title: Blood
Volume: 111
Issue: 5
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2008-03-01
Start Page: 2929
End Page: 2940
Language: English
DOI: 10.1182/blood-2007-06-096602
PUBMED: 18178870
PROVIDER: scopus
PMCID: PMC2254543
Notes: --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus"
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MSK Authors
  1. Theo Daniel Kim
    14 Kim
  2. Glenn Heller
    303 Heller
  3. Christopher King
    29 King
  4. Theis Helge Terwey
    17 Terwey
  5. Odette Marsinay Smith
    95 Smith
  6. David Suh
    41 Suh
  7. Adam Kochman
    45 Kochman
  8. Jeremy Grubin
    10 Grubin