Transplantation of allogeneic T cells alters iron homeostasis in NOD/SCID mice.
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.
Bair
Steven
S
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA
Spaulding
Emily
E
Parkkinen
Jaakko
J
Shulman
Howard M
HM
Lesnikov
Vladimir
V
Beauchamp
Mary
M
Canonne-Hergaux
François
F
Kowdley
Kris V
KV
Deeg
H Joachim
HJ
D019264:Adoptive Transfer / Q000009:adverse effects*; D000818:Animals; D001059:Apoproteins / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000378:metabolism / Q000637:transplantation*; D014168:Transferrin / Q000378:metabolism; D014184:Transplantation, Homologous
D001059:Apoproteins; D014168:Transferrin; C028284:apotransferrin; D007501:Iron