title: Low numbers of CD8+ T lymphocytes in hereditary haemochromatosis are explained by a decrease of the most mature CD8+ effector memory T cells.
abstract: 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 (T(CM)) and effector memory (T(EM)), and further subsets of CD8(+) T(EM) 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 T(EM) cells and the T(EM) CD27(-)CD28(-) subset no effect of age was observed in HH [R(2) = 0.001, not significant (n.s.) and R(2) = 0.01, n.s., respectively] contrasting with the increasing of these subpopulations with age in controls (R(2) = 0.09, P = 0.017 and R(2) = 0.22, P = 0.0005, respectively). Interestingly, patients homozygous for the A-A-T haplotype have lower numbers of CD8(+) T(EM) cells due especially to lower numbers of T(EM) CD27(-)CD28(-) (0.206 +/- 0.119 and 0.066 +/- 0.067 x 10(6) cells/ml, respectively) than patients carrying the G-G-G haplotype (0.358 +/- 0.195 and 0.246 +/- 0.202 x 10(6) cells/ml, respectively). This may suggest an inability of HH patients to differentiate the CD8(+) T cells into the most mature phenotype.
authors.affiliation: Iron Genes and the Immune System (IRIS), IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal. fmacedo@ibmc.up.pt
authors.forename: M F
authors.initials: MF
authors.lastname: Macedo
authors.forename: G
authors.initials: G
authors.lastname: Porto
authors.forename: M
authors.initials: M
authors.lastname: Costa
authors.forename: C P
authors.initials: CP
authors.lastname: Vieira
authors.forename: B
authors.initials: B
authors.lastname: Rocha
authors.forename: E
authors.initials: E
authors.lastname: Cruz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018106:CD28 Antigens; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D005260:Female; D006239:Haplotypes / Q000235:genetics / Q000276:immunology; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D018655:Lymphocyte Count; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D012189:Retrospective Studies; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D018106:CD28 Antigens; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7