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

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.

journal_name

Blood

journal_title

Blood

authors

Bair S,Spaulding E,Parkkinen J,Shulman HM,Lesnikov V,Beauchamp M,Canonne-Hergaux F,Kowdley KV,Deeg HJ

doi

10.1182/blood-2008-09-178517

subject

Has Abstract

pub_date

2009-02-19 00:00:00

pages

1841-4

issue

8

eissn

0006-4971

issn

1528-0020

pii

blood-2008-09-178517

journal_volume

113

pub_type

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