Organ-derived dendritic cells have differential effects on alloreactive T cells Academic Article uri icon

Overview

MeSH Major

  • Dendritic Cells
  • Isoantigens
  • T-Lymphocytes

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 date

  • March 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2254543

Digital Object Identifier (DOI)

  • 10.1182/blood-2007-06-096602

PubMed ID

  • 18178870

Additional Document Info

start page

  • 2929

end page

  • 40

volume

  • 111

number

  • 5