T-cell receptor repertoire in hereditary hemochromatosis:: A study of 32 hemochromatosis patients and 274 healthy subjects

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: V alpha2.3, V beta5.1, V beta5.2, V beta5.3, V beta6.7, V beta8, and V beta 12 among the CD4(+) and CD8(+) populations. Lymphopenias and absence of expansions of the V beta5.2 and V beta 12 chains in the CD8(+) pool were seen in controls heterozygous for the C282Y mutation. Expansions in the control group were seen wit-hin 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 char 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. (C) American Society for Histocompatibility and Immunogenetics, 2001, Published by Elsevier Science Inc.