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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1100-1107
IMMUNOBIOLOGY
Age-related increase of frequency of a new, phenotypically
distinct subpopulation of human peripheral blood T cells expressing
lowered levels of CD4
Ewa Bryl,
Magdalena Gazda,
Jerzy Foerster, and
Jacek M. Witkowski
From the Department of Immunology and the
Department of Pathophysiology, Medical University of Gdansk;
and the Voivodial Outpatient Geriatric Clinic of Gdansk,
Poland.
Aging is associated with modifications of T-cell phenotype and
function, leading to impaired activation in response to both new and
recall antigens. It is not known if T-cell activation results in
elimination of a number of the CD4 molecules from the cell surface, as
is the case with CD3/T-cell receptor complexes, or how aging
influences the process. The T cells of young and elderly donors with
reduced expression of CD4 were examined to see whether these cells
exhibit other phenotypic features suggesting their active
state. It was found that T lymphocytes expressing CD4 can be
divided into 2 semidiscrete subpopulations: the major (CD4+) population, in which the level of expression of CD4
is constant and high, and a minor population (CD4lo), in
which the expression of CD4 can be up to an order of magnitude lower
than on the CD4+ cells. The proportion of CD4lo
cells is age dependent and highly variable in the apparently healthy
human population, with the expression of CD4 ranging from around 10%
of all peripheral blood lymphocytes in the young to more than 30% in
the elderly. Lowered expression of CD4 is correlated with a reduced
expression of CD3, as well as with a decreased amount of CD28 and
CD95Fas. Activation of CD4lo cells is suggested by their
expression of CD25 and increased amounts of HLA-DR. Phenotypic
characteristics of the CD4lo T-cell subpopulation suggest
that it might be formed by (perhaps chronically) activated, temporarily
apoptosis-resistant cells, possibly accumulating in the elderly.
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