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 genotyp e/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 s ubjects 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 t he 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 s een wit-hin the CD8(+) pool and were rare/absent within the CD4(+) pool. Tc R expansions were found more frequent in patients with iron overload relate d pathology than in patients without pathology. 9/16 of the patients with p athology have at least one expansion among the CD8(+) pool a number signifi cantly higher compared with patients without pathology (1/16), These findin gs suggest char Hfe has an effect in the shaping of T-cell populations eith er directly, as indicated by the lymphopenia seen in the two chains in C282 Y heterozygous without iron overload, or indirectly by contributing to iron overload pathology. (C) American Society for Histocompatibility and Immuno genetics, 2001, Published by Elsevier Science Inc.