Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28- T cells.
The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28- T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population 'to expand', coinciding with an 'expansion' of CD8+ CD28- T cells in peripheral blood of HLA-A3+ but not HLA-A3- HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28- T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH.
Arosa
F A
FA
Department of Molecular Immunology and Pathology, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Portugal.
Oliveira
L
L
Porto
G
G
da Silva
B M
BM
Kruijer
W
W
Veltman
J
J
de Sousa
M
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015791:HLA-A3 Antigen / Q000276:immunology*; D006432:Hemochromatosis / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged
D015415:Biomarkers; D018106:CD28 Antigens; D016827:CD8 Antigens; D015791:HLA-A3 Antigen