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*
Laboratory of Immunology, Divisions of Geriatrics and Gerontology and International Medicine and Infectious Diseases, Cornell University Medical College, New York, NY 10021; and
Section of Immunology and Inflammation, Hospital for Special Surgery, New York, NY 10021
During human aging, one of the major changes in the T cell
repertoire is a dramatic expansion of T cells with the atypical
CD28-CD8+ phenotype. In this study, we show
that this increase is a consequence not only of an expansion in the
CD28-CD8+ population but also of a decrease in
the number of CD28+CD8+ T cells. The decrease
in circulating CD28+CD8+ T cells is
dramatically accelerated after the age of 50 and is not accompanied by
an equivalent reduction in the CD28+CD4+
subset. Our findings confirm that aging leads to an accumulation of
CD45RO+ T cells within the
CD28+CD8+ subset as previously observed.
Surprisingly, we found an increase in CD45RA+ expression
with age in the CD28-CD8+ subset.
Immune-phenotyping for activation markers, measurement of telomere DNA
content, and cytokine production analysis indicate that the large
majority of CD28-CD8+ T cells are
Ag-experienced, despite their CD45RA+ phenotype. Our study
further demonstrates that the poor proliferative response displayed by
CD28-CD8+ T cells is not a consequence of
telomere shortening. Also, analysis of cytokine production at the
single cell level revealed that the proportions of
IFN-
+, IL-4+, and IL-10+ T cells
are considerably higher among the CD28-CD8+
than the CD28+CD8+ subset. In summary, these
data explain the presence of CD45RA+ T cells in the
elderly, shed light on the phylogenetic origin of
CD28-CD8+ T cells, and suggest a role for
these cells in the immune senescence process.
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