title: T-cell receptor repertoire in hereditary hemochromatosis: a study of 32 hemochromatosis patients and 274 healthy subjects.
abstract: Low CD8(+) T lymphocyte numbers have contributed to deciphering the genotype/phenotype discrepancies found in hereditary hemochromatosis (HH) patients genotyped for the Hfe mutations, C282Y and H63D. In this study, we extend the analysis of T lymphocytes in HH to the T cell receptor (TcR) repertoire. Thirty-two HH patients (C282Y homozygous) and 274 Hfe genotyped healthy subjects were studied. The following TcR chains were analyzed: Valpha2.3, Vbeta5.1, Vbeta5.2, Vbeta5.3, Vbeta6.7, Vbeta8, and Vbeta12 among the CD4(+) and CD8(+) populations. Lymphopenias and absence of expansions of the Vbeta5.2 and Vbeta12 chains in the CD8(+) pool were seen in controls heterozygous for the C282Y mutation. Expansions in the control group were seen within the CD8(+) pool and were rare/absent within the CD4(+) pool. TcR expansions were found more frequent in patients with iron overload related pathology than in patients without pathology. 9/16 of the patients with pathology have at least one expansion among the CD8(+) pool a number significantly higher compared with patients without pathology (1/16). These findings suggest that Hfe has an effect in the shaping of T-cell populations either directly, as indicated by the lymphopenia seen in the two chains in C282Y heterozygous without iron overload, or indirectly by contributing to iron overload pathology.
authors.affiliation: Molecular Immunology and Pathology, ICBAS and Molecular Immunology, IBMC, Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Cardoso
authors.forename: G
authors.initials: G
authors.lastname: Porto
authors.forename: R
authors.initials: R
authors.lastname: Lacerda
authors.forename: D
authors.initials: D
authors.lastname: Resende
authors.forename: P
authors.initials: P
authors.lastname: Rodrigues
authors.forename: F
authors.initials: F
authors.lastname: Bravo
authors.forename: J C
authors.initials: JC
authors.lastname: Oliveira
authors.forename: B
authors.initials: B
authors.lastname: Justiça
authors.forename: M
authors.initials: M
authors.lastname: de Sousa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000276:immunology; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics* / Q000276:immunology; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000378:metabolism; D019190:Iron Overload; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D007501:Iron