title: Invariant Natural Killer T Cells are Reduced in Hereditary Hemochromatosis Patients.
abstract: OBJECTIVE
  Invariant natural killer T (iNKT) cells are CD1d restricted-T cells that react to lipid antigens. iNKT cells were shown to be important in infection, autoimmunity and tumor surveillance. Alterations in the number and function of these cells were described in several pathological conditions including autoimmune and/or liver diseases. CD1d is critical for antigen presentation to iNKT cells, and its expression is increased in liver diseases. The liver is the major organ affected in Hereditary Hemochromatosis (HH), an autosomal recessive disorder caused by excessive iron absorption. Herein, we describe the study of iNKT cells of HH patients.
  
  
  METHODS
  Twenty-eight HH patients and 24 control subjects from Santo António Hospital, Porto, were included in this study. Patient's iron biochemical parameters (serum transferrin saturation and ferritin levels) and the liver function marker alanine transaminase (ALT) were determined at the time of study. Peripheral blood iNKT cells were analyzed by flow cytometry using an anti-CD3 antibody and the CD1d tetramer loaded with PBS57.
  
  
  RESULTS
  We found a decrease in the percentage and number of circulating iNKT cells from HH patients when compared with control population independently of age. iNKT cell defects were more pronounced in untreated patients, relating with serum ferritin and transferrin saturation levels. No correlation was found with ALT, a marker of active liver dysfunction.
  
  
  CONCLUSIONS
  Altogether, our results demonstrate that HH patients have reduced numbers of iNKT cells and that these are influenced by iron overload.
authors.affiliation: UniLiPe, IBMC-Institute for Molecular and Cellular Biology, University Porto, Porto, Portugal.
authors.forename: M L
authors.initials: ML
authors.lastname: Maia
authors.affiliation: UniLiPe, IBMC-Institute for Molecular and Cellular Biology, University Porto, Porto, Portugal.
authors.forename: C S
authors.initials: CS
authors.lastname: Pereira
authors.affiliation: Clinical Hematology, CHP-HSA-Santo António General Hospital Porto, Porto, Portugal.
authors.forename: G
authors.initials: G
authors.lastname: Melo
authors.affiliation: UniLiPe, IBMC-Institute for Molecular and Cellular Biology, University Porto, Porto, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Pinheiro
authors.affiliation: University of Manchester, Manchester, UK.|Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Exley
authors.affiliation: Clinical Hematology, CHP-HSA-Santo António General Hospital Porto, Porto, Portugal.|BCRIB, IBMC-Institute for Molecular and Cellular Biology and ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Porto, Portugal.
authors.forename: G
authors.initials: G
authors.lastname: Porto
authors.affiliation: UniLiPe, IBMC-Institute for Molecular and Cellular Biology, University Porto, Porto, Portugal. fmacedo@ibmc.up.pt.|Aveiro Health Sciences Program, University of Aveiro, Aveiro, Portugal. fmacedo@ibmc.up.pt.
authors.forename: M F
authors.initials: MF
authors.lastname: Macedo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology*
chemical_list: D005293:Ferritins; D007501:Iron; D000410:Alanine Transaminase
keywords: Invariant natural killer T cells; hereditary hemochromatosis; iron; lipid