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mented that telomere lengths of total PBMC from HIV-infected individuals
shortened at an accelerated rate compared with age-matched seronegative con-
trols (Wolthers et al., 1996). For HIV-infected individuals, the mean TRF
length loss in the progressors (175 G 105 bp/yr) was greater than that in the
asymptomatic individuals (114 G 100 bp/yr), and both were signi®cantly in-
creased compared with healthy controls (4.7 G 71 bp/yr). These data indicate
that increased cell division of immune cells is associated with HIV infection and
correlates with disease status.
Telomere length measurements on de®ned cell populations separated by cell
sorting procedures have provided further insight into HIV disease pathogenesis.
Several groups compared telomere lengths of the two T-cell subsets. In four
independent studies, telomere shortening was consistently observed within the
CD8 T-cell subset, with only minimal or no telomere shortening in the CD4
subset. In one study, sequential samples from several individuals demonstrated
progressive CD8 T-cell telomere shortening over time ( Wolthers et al., 1996).
In another study, the CD8 T cells were further sorted, permitting the demon-
stration that within the CD8 subset, all of the telomere shortening could be
accounted for by the cells that lacked CD28 expression ( E¨ros et al., 1996). In
fact, the telomere lengths of the CD8
CD28
ÿ
T cells were the same size as
those of centenarian lymphocytes, suggestive of accelerated immunological ag-
ing during HIV disease. Boussin and colleagues (Pommier et al., 1997) have also
documented CD8 telomere shortening and, furthermore, provide data showing
that B-cell telomeres shorten as well, consistent with the well-documented hy-
peractivation and polyclonal antibody production observed during HIV infec-
tion. Finally, a novel approach to telomere analysis in the two T-cell subsets
was used by Hodes and colleagues (Palmer et al., 1997) in an e¨ort to eliminate
the variability inherent in telomere lengths in outbred human populations by
comparing cell populations derived from HIV-discordant identical twins. These
studies showed that the mean TRF of the CD8 T cells was shorter in HIV-
infected versus uninfected twins (mean di¨erence 1.1 G 0.7 kb). Thus, accel-
erated telomere shortening in CD8 T cells during HIV disease has been an
unequivocal observation in all of the published studies that have used this ex-
perimental approach.
Numerous studies have been performed in an e¨ort to elucidate CD4 T-cell
dynamics in HIV disease, but, in marked contrast to the CD8 T-cell ®ndings,
the results have been inconsistent, showing an entire spectrum of changes, pos-
sibly suggesting a more complicated picture. For example, in the same twin
study in which CD8 T-cell telomeres were shorter in the infected twin, Palmer
et al. (Palmer et al., 1997) demonstrated the CD4 T cells in the HIV-infected
twins were longer than those in the uninfected twin (mean di¨erence 0.9 G 0.4
kb). Furthermore, the CD4 T-cell subset showed no di¨erence in the total
number of population doublings achieved in long-term culture between the
HIV-infected versus uninfected twins. The data from these studies were inter-
preted to indicate that the immune de®ciency associated with HIV disease could
not be attributed to exhaustion of the replicative potential of CD4 T cells. Even
in studies that do document some CD4 T-cell telomere shortening, these
