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
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-41949131652&partnerID=40&md5=a41bbeac9da07357df88ec992aa2ab68
Notes:	--- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus"