Invariant Natural Killer T Cells are Reduced in Hereditary Hemochromatosis Patients

Abstract

Purpose

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.

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Acknowledgments

This work was supported by Fundação para a Ciência e a Tecnologia (PEST-C/SAU/LA0002/2013 - FCOMP-01-0124-FEDER-037277) and by FEDER Funds through the Operational Competitiveness Programme — COMPETE and by National Funds through FCT — Fundação para a Ciência e a Tecnologia under the project FCOMP-01-0124-FEDER-015955 (PTDC/SAU-ORG/110112/2009). MAE was partially supported by NIH grant CA170194. CSP was supported by a fellowship from Fundação para a Ciência e Tecnologia (SFRH/BD/79211/2011). The authors would like to thank the NIH Tetramer Core, Emory University, USA, for providing the CD1d-PBS57 tetramer.

Conflicts of Interest

The authors declare that they have no conflict of interest.

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Correspondence to M. F. Macedo.

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Maia, M.L., Pereira, C.S., Melo, G. et al. Invariant Natural Killer T Cells are Reduced in Hereditary Hemochromatosis Patients. J Clin Immunol 35, 68–74 (2015). https://doi.org/10.1007/s10875-014-0118-0

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Keywords

  • Invariant natural killer T cells
  • hereditary hemochromatosis
  • iron
  • lipid