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Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
With advancing age the CD4+ T lymphocyte compartment
becomes enriched for memory cells in both humans and experimental
animals. Although it has been assumed that the shift from a naive to a
memory-dominant population is due to a lifetime of antigenic exposure
and selection as well as a loss of naive cell input due to reduced
thymopoiesis, the present data suggest that the aged microenvironment
influences the maturation of newly produced CD4+ T cells.
In two models, aged and young mice were compared for the ability to
reconstitute their peripheral CD4+ T cell pools following
depletion, and both age groups were found to be competent to renew this
population. However, the phenotype and lymphokine profile of
populations arising in aged animals were distinctly different from
those in the young mice. In contrast to the expectation that depletion
and reconstitution might give rise to a naive-dominant T cell pool,
aged mice reconstituted a population nearly indistinguishable from that
found in control age-matched individuals. The majority of the
CD4+ pool were CD44high CD45RBlow
Mel-14low and upon activation with anti-CD3 these
CD4+ T cells produced mRNA for IL-2, IL-4, IL-5, and
IFN-
. In aged bone marrow-transplanted mice, the same phenotypic
profile and cytokine mRNA pattern were found in CD4+ T
cells of host and donor origin. In contrast, the majority of
CD4+ T cells in young reconstituted mice were
CD44low CD45RBhigh Mel-14high.
These lymphocytes, when activated, produced high levels of mRNA for
IL-2, with little or no IL-4, IL-5, or IFN-
mRNA.
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