immunological senescence revealed

Doug Skrecky oberon at vcn.bc.ca
Sat Jun 10 11:19:51 EST 2000

Shortage of circulating naive CD8+ T cells provides 
insights on immunodeficiency in aging.

Blood 95: 2860-2868 2000


    Clinical obervations indicate that elderly people are
prone to severe, often lethal infectious diseases induced
by novel pathogens. Since the ability to mount primary
immune responses relies on the availability of naive T
cells, the circulating naive T-cell reservoir was evaluated
throughout the human life span. Naive T cells were identified
as CD95- T lymphocytes for their phenotypic and functional
features. Indeed, the lack of CD95 marker is sufficient to
identify a population of naive T cells, as defined by
coincidence with previously characterized CD45RA+
CD62L+ T cells. Naive CD95- T cells, as expected,
require a costimulatory signal, such as CD28, to optimally
proliferate after anti-CD3 stimulation. Cytofluorimetric
analysis of circulating T lymphocytes from 120 healthy
subjects ranging in age from 18 to 105 years revealed
that naive T cells decreased sharply with age. the
younger subjects had a naive T-lymphocyte count of
177 +-28 cells/microL. Surprisingly, the naive T-cell
count was lower in CD8+ than in CD4+ subsets at any
age, and the oldest individuals were almost completely
depleted of circulating naive CD8+ T cells (13 +-4 cells/microL).
Concomitantly, a progressive expansion of CD28- T cells
occurs with age, which can be interpreted as a compensatory
mechanism. These data provide new insights into age
related T-cell-mediated immunodeficiency and reveal
some analogies of T-cell dynamics between advanced
aging and human immunodeficiency virus (HIV) infection.
In conclusion, the exhaustion of the naive CD8+ T-cell
reservoir, which has never been reported before, suggests
that this T-cell pool is a major target of the aging process
and may define a parameter possibly related to the life
span of humans.

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