Submitted September 11, 2008
Accepted December 11, 2008
Transplantation of allogeneic T-cells alters iron homeostasis in NOD/SCID mice
Steven Bair, Emily Spaulding, Jaakko Parkkinen, Howard M. Shulman, Vladimir Lesnikov, Mary Beauchamp, Francois Canonne-Hergaux, Kris V Kowdley, and H. Joachim Deeg*
Fred Hutchinson Cancer Research Center, Seattle, WA, United States
University of Washington, Seattle, WA, United States
Benaroya Research Institute at Virginia Mason, Seattle, WA, United States
Institut de Chimie des Substances Naturelles, (ICSN), CNRS, Gif-Sur-Yvette, France
* Corresponding author; email: jdeeg{at}fhcrc.org.
Iron overload is common in patients undergoing allogeneic hematopoietic cell transplantation (HCT), but the mechanisms leading to overload are unknown. Here, we determined iron levels and the expression of iron regulatory proteins in the liver and gut of NOD/SCID mice transplanted with syngeneic (histocompatible) or allogeneic (histoincompatible) T lymphocytes. Infusion of histoincompatible T cells resulted in a significant rise in serum iron levels and liver iron content. Iron deposition was accompanied by hepatocyte injury and intestinal villous damage. Feeding of low or high iron diet was associated with appropriate ferroportin 1 and hepcidin responses in mice given histocompatible T cells, while mice given histoincompatible T cells showed inappropriate upregulation of duodenal ferroportin 1 and a loss of expression of hepatic hepcidin. These findings suggest that alloreactive T cell-dependent signals induced dysregulation of intestinal iron absorption, which contributed to liver iron overload after HCT.
