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ugich*,ugich2,*,,
*
Laboratory of T Cell Development, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021;
Division of Geriatrics and Gerontology, Department of Medicine, Weill Medical College of Cornell University, and
Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021
Relative diversity and representation of peripheral T cells bearing
different TCR Vß families are remarkably tightly regulated between
birth and advanced adulthood. By contrast, individual elderly humans
and C3H.SW and B10.BR aged mice display drastic disruption in such
regulation. It was suggested that the alterations in the murine aged T
cell compartment were due to age-related clonal T cell expansions
(TCE). Here, we studied the kinetics of homeostatic dysregulation of T
cell populations in aged C57BL/6 (B6) mice. Using mAb staining, we show
that the percentages of 
ß+CD8+ or
CD4+ T cells bearing different TCRVß elements remain
virtually constant in mice up to 12 mo of age. In 22-mo-old mice,
however, there is a dramatic disturbance of this pattern owing to the
emergence of CD8+ TCE. Expanded T cells did not show any
obvious bias in Vß usage and were derived in all cases examined thus
far from a single clone. TCE appeared later in life, compared with B
cell clonal expansions. However, and in contrast to those detected in
humans, TCE were frequently unstable disappearing within 2–4 mo, with
other TCE appearing within the same time frame. Additional studies
carried on thymic T cells, thymectomized mice, and young T transferred
cells into Rag1-/- mice suggest that the clonal
expansions occur in the periphery and that their onset is accelerated
by decreased thymic output and/or function(s).
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