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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2860-2868
Shortage of circulating naive CD8+ T cells provides
new insights on immunodeficiency in aging
Francesco F. Fagnoni,
Rosanna Vescovini,
Giovanni Passeri,
Giovanni Bologna,
Mario Pedrazzoni,
Giampaolo Lavagetto,
Amos Casti,
Claudio Franceschi,
Mario Passeri, and
Paolo Sansoni
From the Department of Internal Medicine and Biomedical Sciences and
the Institute of Biological Chemistry, University of Parma, Parma,
Italy; the Department of Experimental Pathology, University of Bologna,
Bologna, Italy; and INRCA (the National Institute for
Research and Care for Elderly), Ancona, Italy.
Clinical observations 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 825 ± 48 cells/µL, and the
centenarians had a naive T-lymphocyte count of 177 ± 28 cells/µL.
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/µL). 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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|
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175(3):
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|
|
|
|
|
|
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|
|
|
|
|
|
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K. Argentati, F. Re, A. Donnini, M. G. Tucci, C. Franceschi, B. Bartozzi, G. Bernardini, and M. Provinciali
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|
|
|
|
|
|
|
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1085 - 1085.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gioia, C. Agrati, R. Casetti, C. Cairo, G. Borsellino, L. Battistini, G. Mancino, D. Goletti, V. Colizzi, L. P. Pucillo, et al.
Lack of CD27-CD45RA-V{gamma}9V{delta}2+ T Cell Effectors in Immunocompromised Hosts and During Active Pulmonary Tuberculosis
J. Immunol.,
February 1, 2002;
168(3):
1484 - 1489.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-i. Yasunaga, T. Sakai, K. Nosaka, K.-i. Etoh, S. Tamiya, S. Koga, S. Mita, M. Uchino, H. Mitsuya, and M. Matsuoka
Impaired production of naive T lymphocytes in human T-cell leukemia virus type I-infected individuals: its implications in the immunodeficient state
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May 15, 2001;
97(10):
3177 - 3183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
