Open AccessAnomalies of the CD8 + T cell pool in haemochromatosis: HLA‐A3‐linked expansions of CD8 + CD28 − T cells
Author(s) -
AROSA F. A.,
OLIVEIRA L.,
PORTO G.,
DA SILVA B. M.,
KRUIJER W.,
VELTMAN J.,
DE SOUSA M.
Publication year - 1997
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1997.d01-967.x
Subject(s) - cytotoxic t cell , cd8 , cd28 , immunology , ctl* , biology , t cell , peripheral blood mononuclear cell , population , phytohaemagglutinin , human leukocyte antigen , antigen , immune system , medicine , in vitro , genetics , environmental health
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 51 Cr‐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.