Haemochromatosis as a window into the study of the immunological system: A novel correlation between CD8⁺ lymphocytes and iron overload

Abstract

In the present study we report a serial investigation of the numbers of the peripheral blood cells — erythrocytes, polymorphonuclear neutrophils, total lymphocytes, T‐lymphocyte subpopulations (CD2, CD4, CD8), B lymphocytes and monocytes — in a group of 21 patients with haemochromatosis during the time of intensive phlebotomy treatment, i.e., from iron overload until the onset of iron deficiency. A remarkable individual stability of all blood cell populations studied was found in all patients. Patients differed in their relative proportions of CD4+ and CD8+. Each individual's CD4/CD8 ratio, as well as the absolute numbers, remained unaffected with time, confirming the existence of a strict homeostatic regulation of the relative numbers of the two major peripheral T lymphocytes. A significant positive correlation between CD4/CD8 ratios and the amount of iron mobilised by phlebotomy was found during this study. A novel correlation between the relative proportions of CD4+ and CD8+ cells and iron overload is confirmed by the follow‐up of iron re‐entry in the serum transferrin pool in the treated patients.

The detrimental effects of iron on the joint: a comparison between haemochromatosis and haemophilia

“…An iron-rich environment is favourable for bacterial growth, affects the gut microbiota,77 and impairs the function of different immune cells. The phagocytic function of neutrophils is inhibited,78 T cell surface molecule expression is modulated, impairing T cell recognition and activation,79 and a decrease in circulating lymphocytes is suggested, but not observed consistently 80 81. In HH, the mutation in HFE, an MHC class I-like molecule, is also thought to impair antigen presentation 82.…”

ER Stress and Iron Homeostasis: A New Frontier for the UPR

“…Accordingly, higher CD4 + /CD8 + ratios [12], later attributed to defective numbers of CD8 + T cells [13], were consistently found in HH subjects in comparison to control individuals. Complementing these data, increased clinical severity of the disease was observed in the context of a lower CD8 + T lymphocyte pool [14].…”

The role of MHC class Ib-restricted T cells during infection

“…A role for CD8 + T cells was initially proposed because many HH patients have unusually small CD8 + T cell populations in circulation (Macedo et al 2010; Porto et al 1994). However, the exact nature of this deficiency is unclear, as it could be an indirect result of iron overload or a direct result of HFE regulating CD8 + T cells (Costa et al 2015; Reuben et al 2014).…”