Transplantation of allogeneic T cells alters iron homeostasis in NOD/SCID mice.

Publication Type:

Journal Article

Source:

Blood, Volume 113, Issue 8, p.1841-4 (2009)

Keywords:

2009, Adoptive Transfer, Animals, Apoproteins, Center-Authored Paper, Clinical Research Division, Comparative Medicine Core Facility, Experimental Histopathology Core Facility, homeostasis, Iron, Iron Overload, MICE, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Shared Resources, Specialized Pathology Core Facility, Specimen Processing Core Facility, T-Lymphocytes, Transferrin, Transplantation, Homologous

Abstract:

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 nonobese diabetic-severe combined immunodeficient (NOD/SCID) mice that underwent transplantation 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, whereas mice given histoincompatible T cells showed inappropriate up-regulation 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.