Abstract
The dynamic basis for T-cell depletion in late-stage HIV-1 disease remains controversial. Using a new, non-radioactive, endogenous labeling technique, we report direct measurements of circulating T-cell kinetics in normal and in HIV-1-infected humans. In healthy, HIV-1-seronegative subjects, CD4+ and CD8+ T cells had half-lives of 87 days and 77 days, respectively, with absolute production rates of 10 CD4+ T cells/μl per day and 6 CD8+ T cells/μl per day. In untreated HIV-1-infected subjects (with a mean CD4 level of 342 cells/μl), the half-life of each subpopulation was less than 1/3 as long as those of healthy, HIV-1-seronegative subjects but was not compensated by an increased absolute production rate of CD4+ T cells. After viral replication was suppressed by highly active antiretroviral therapy for 12 weeks, the production rates of circulating CD4+ and CD8+ T cells were considerably elevated; the kinetic basis of increased CD4 levels was greater production, not a longer half-life, of circulating cells. These direct measurements indicate that CD4+ T-cell lymphopenia is due to both a shortened survival time and a failure to increase the production of circulating CD4+ T cells. Our results focus attention on T-cell production systems in the pathogenesis of HIV-1 disease and the response to antiretroviral therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 83-89 |
| Number of pages | 7 |
| Journal | Nature Medicine |
| Volume | 5 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 2 1999 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans. / Hellerstein, M.; Hanley, M. B.; Cesar, D.; Siler, S.; Papageorgopoulos, C.; Wieder, Eric; Schmidt, D.; Hoh, R.; Neese, R.; Macallan, D.; Deeks, S.; Mccune, J. M.
In: Nature Medicine, Vol. 5, No. 1, 02.02.1999, p. 83-89.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans
AU - Hellerstein, M.
AU - Hanley, M. B.
AU - Cesar, D.
AU - Siler, S.
AU - Papageorgopoulos, C.
AU - Wieder, Eric
AU - Schmidt, D.
AU - Hoh, R.
AU - Neese, R.
AU - Macallan, D.
AU - Deeks, S.
AU - Mccune, J. M.
PY - 1999/2/2
Y1 - 1999/2/2
N2 - The dynamic basis for T-cell depletion in late-stage HIV-1 disease remains controversial. Using a new, non-radioactive, endogenous labeling technique, we report direct measurements of circulating T-cell kinetics in normal and in HIV-1-infected humans. In healthy, HIV-1-seronegative subjects, CD4+ and CD8+ T cells had half-lives of 87 days and 77 days, respectively, with absolute production rates of 10 CD4+ T cells/μl per day and 6 CD8+ T cells/μl per day. In untreated HIV-1-infected subjects (with a mean CD4 level of 342 cells/μl), the half-life of each subpopulation was less than 1/3 as long as those of healthy, HIV-1-seronegative subjects but was not compensated by an increased absolute production rate of CD4+ T cells. After viral replication was suppressed by highly active antiretroviral therapy for 12 weeks, the production rates of circulating CD4+ and CD8+ T cells were considerably elevated; the kinetic basis of increased CD4 levels was greater production, not a longer half-life, of circulating cells. These direct measurements indicate that CD4+ T-cell lymphopenia is due to both a shortened survival time and a failure to increase the production of circulating CD4+ T cells. Our results focus attention on T-cell production systems in the pathogenesis of HIV-1 disease and the response to antiretroviral therapy.
AB - The dynamic basis for T-cell depletion in late-stage HIV-1 disease remains controversial. Using a new, non-radioactive, endogenous labeling technique, we report direct measurements of circulating T-cell kinetics in normal and in HIV-1-infected humans. In healthy, HIV-1-seronegative subjects, CD4+ and CD8+ T cells had half-lives of 87 days and 77 days, respectively, with absolute production rates of 10 CD4+ T cells/μl per day and 6 CD8+ T cells/μl per day. In untreated HIV-1-infected subjects (with a mean CD4 level of 342 cells/μl), the half-life of each subpopulation was less than 1/3 as long as those of healthy, HIV-1-seronegative subjects but was not compensated by an increased absolute production rate of CD4+ T cells. After viral replication was suppressed by highly active antiretroviral therapy for 12 weeks, the production rates of circulating CD4+ and CD8+ T cells were considerably elevated; the kinetic basis of increased CD4 levels was greater production, not a longer half-life, of circulating cells. These direct measurements indicate that CD4+ T-cell lymphopenia is due to both a shortened survival time and a failure to increase the production of circulating CD4+ T cells. Our results focus attention on T-cell production systems in the pathogenesis of HIV-1 disease and the response to antiretroviral therapy.
UR - http://www.scopus.com/inward/record.url?scp=17444379333&partnerID=8YFLogxK
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U2 - 10.1038/4772
DO - 10.1038/4772
M3 - Article
VL - 5
SP - 83
EP - 89
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 1
ER -