Low numbers of CD8+ T lymphocytes in hereditary haemochromatosis are explained by a decrease of the most mature CD8+ effector memory T cells

Abstract

Summary Low CD8+ T lymphocyte numbers have long been described in hereditary haemochromatosis (HH). Recently, two conserved haplotypes localized near the microsatellite D6S105 at the major histocompatibility complex (MHC) class I region were described predicting the clinical expression of HH and the CD8+ T lymphocyte numbers. The A-A-T haplotype was associated with a severe clinical expression of HH and low CD8+ T lymphocyte numbers, while the G-G-G haplotype was associated with a milder clinical expression of HH and high CD8+ T lymphocyte numbers. As CD8+ T lymphocytes are a very heterogeneous population, in this study we analysed the CD8+ subpopulations of naive, central memory (TCM) and effector memory (TEM), and further subsets of CD8+ TEM cells in 47 HH patients and 68 controls. In addition, association studies were conducted between the conserved haplotypes and the CD8+ T cell subpopulations in HH. Variations of the numbers of naive and central memory cells with age were similar between HH patients and controls. For TEM cells and the TEM CD27-CD28- subset no effect of age was observed in HH [R2 = 0.001, not significant (n.s.) and R2 = 0.01, n.s., respectively] contrasting with the increasing of these subpopulations with age in controls (R2 = 0.09, P = 0.017 and R2 = 0.22, P = 0.0005, respectively). Interestingly, patients homozygous for the A-A-T haplotype have lower numbers of CD8+ TEM cells due especially to lower numbers of TEM CD27-CD28- (0.206 ± 0.119 and 0.066 ± 0.067 × 106 cells/ml, respectively) than patients carrying the G-G-G haplotype (0.358 ± 0.195 and 0.246 ± 0.202 × 106 cells/ml, respectively). This may suggest an inability of HH patients to differentiate the CD8+ T cells into the most mature phenotype.