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

Blood. 2008 Mar 1;111(5):2929-40. doi: 10.1182/blood-2007-06-096602. Epub 2008 Jan 4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Gene Expression Profiling
  • Graft vs Host Disease
  • Humans
  • Integrins / metabolism
  • Isoantigens / immunology*
  • Ligands
  • Lipopolysaccharides / pharmacology
  • Liver / cytology
  • Liver / drug effects
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity / drug effects
  • Phenotype
  • Receptors, Lymphocyte Homing / genetics
  • Receptors, Lymphocyte Homing / metabolism
  • Selectins / metabolism
  • Survival Rate
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Integrins
  • Isoantigens
  • Ligands
  • Lipopolysaccharides
  • Receptors, Lymphocyte Homing
  • Selectins
  • integrin alpha4beta7