Factors influencing T-cell turnover in HIV-1-seropositive patients

Joseph M. McCune, Mary Beth Hanley, Denise Cesar, Robert Halvorsen, Rebecca Hoh, Diane Schmidt, Eric Wieder, Steven Decks, Scott Siler, Richard Neese, Marc Hellerstein

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

HIV-1 disease is associated with pathological effects on T-cell production, destruction, and distribution. Using the deuterated (2H) glucose method for endogenous labeling, we have analyzed host factors that influence T-cell turnover in HIV-1-uninfected and -infected humans. In untreated HIV-1 disease, the average half life of circulating T cells was diminished without compensatory increases in cell production. Within 12 weeks of the initiation of highly active antiretroviral therapy (HAART), the absolute production rates of circulating T cells increased, and normal half-lives and production rates were restored by 12-36 months. Interpatient heterogeneity in the absolute degree of turnover correlated with the relative proportion of naive- and memory/effector-phenotype T cells in each of the CD4+ and CD8+ populations. The half-lives of naive-phenotype T cells ranged from 116-365 days (fractional replacement rates of 0.19-0.60% per day), whereas memory/effector-phenotype T cells persisted with half-lives from 22-79 days (fractional replacement rates of 0.87-3.14% per day). Naive-phenotype T cells were more abundant, and the half-life of total T cells was prolonged in individuals with abundant thymic tissue, as assessed by computed tomography. Such interpatient variation in T-cell kinetics may be reflective of differences in functional immune reconstitution after treatment for HIV-1 disease.

Original languageEnglish
JournalJournal of Clinical Investigation
Volume105
Issue number5
StatePublished - Mar 1 2000
Externally publishedYes

Fingerprint

TCF Transcription Factors
HIV-1
T-Lymphocytes
Phenotype
Half-Life
Highly Active Antiretroviral Therapy
Tomography
Glucose

ASJC Scopus subject areas

  • Medicine(all)

Cite this

McCune, J. M., Hanley, M. B., Cesar, D., Halvorsen, R., Hoh, R., Schmidt, D., ... Hellerstein, M. (2000). Factors influencing T-cell turnover in HIV-1-seropositive patients. Journal of Clinical Investigation, 105(5).

Factors influencing T-cell turnover in HIV-1-seropositive patients. / McCune, Joseph M.; Hanley, Mary Beth; Cesar, Denise; Halvorsen, Robert; Hoh, Rebecca; Schmidt, Diane; Wieder, Eric; Decks, Steven; Siler, Scott; Neese, Richard; Hellerstein, Marc.

In: Journal of Clinical Investigation, Vol. 105, No. 5, 01.03.2000.

Research output: Contribution to journalArticle

McCune, JM, Hanley, MB, Cesar, D, Halvorsen, R, Hoh, R, Schmidt, D, Wieder, E, Decks, S, Siler, S, Neese, R & Hellerstein, M 2000, 'Factors influencing T-cell turnover in HIV-1-seropositive patients', Journal of Clinical Investigation, vol. 105, no. 5.
McCune JM, Hanley MB, Cesar D, Halvorsen R, Hoh R, Schmidt D et al. Factors influencing T-cell turnover in HIV-1-seropositive patients. Journal of Clinical Investigation. 2000 Mar 1;105(5).
McCune, Joseph M. ; Hanley, Mary Beth ; Cesar, Denise ; Halvorsen, Robert ; Hoh, Rebecca ; Schmidt, Diane ; Wieder, Eric ; Decks, Steven ; Siler, Scott ; Neese, Richard ; Hellerstein, Marc. / Factors influencing T-cell turnover in HIV-1-seropositive patients. In: Journal of Clinical Investigation. 2000 ; Vol. 105, No. 5.
@article{9c013521fe16456e8cde2c1ddd9e978c,
title = "Factors influencing T-cell turnover in HIV-1-seropositive patients",
abstract = "HIV-1 disease is associated with pathological effects on T-cell production, destruction, and distribution. Using the deuterated (2H) glucose method for endogenous labeling, we have analyzed host factors that influence T-cell turnover in HIV-1-uninfected and -infected humans. In untreated HIV-1 disease, the average half life of circulating T cells was diminished without compensatory increases in cell production. Within 12 weeks of the initiation of highly active antiretroviral therapy (HAART), the absolute production rates of circulating T cells increased, and normal half-lives and production rates were restored by 12-36 months. Interpatient heterogeneity in the absolute degree of turnover correlated with the relative proportion of naive- and memory/effector-phenotype T cells in each of the CD4+ and CD8+ populations. The half-lives of naive-phenotype T cells ranged from 116-365 days (fractional replacement rates of 0.19-0.60{\%} per day), whereas memory/effector-phenotype T cells persisted with half-lives from 22-79 days (fractional replacement rates of 0.87-3.14{\%} per day). Naive-phenotype T cells were more abundant, and the half-life of total T cells was prolonged in individuals with abundant thymic tissue, as assessed by computed tomography. Such interpatient variation in T-cell kinetics may be reflective of differences in functional immune reconstitution after treatment for HIV-1 disease.",
author = "McCune, {Joseph M.} and Hanley, {Mary Beth} and Denise Cesar and Robert Halvorsen and Rebecca Hoh and Diane Schmidt and Eric Wieder and Steven Decks and Scott Siler and Richard Neese and Marc Hellerstein",
year = "2000",
month = "3",
day = "1",
language = "English",
volume = "105",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "5",

}

TY - JOUR

T1 - Factors influencing T-cell turnover in HIV-1-seropositive patients

AU - McCune, Joseph M.

AU - Hanley, Mary Beth

AU - Cesar, Denise

AU - Halvorsen, Robert

AU - Hoh, Rebecca

AU - Schmidt, Diane

AU - Wieder, Eric

AU - Decks, Steven

AU - Siler, Scott

AU - Neese, Richard

AU - Hellerstein, Marc

PY - 2000/3/1

Y1 - 2000/3/1

N2 - HIV-1 disease is associated with pathological effects on T-cell production, destruction, and distribution. Using the deuterated (2H) glucose method for endogenous labeling, we have analyzed host factors that influence T-cell turnover in HIV-1-uninfected and -infected humans. In untreated HIV-1 disease, the average half life of circulating T cells was diminished without compensatory increases in cell production. Within 12 weeks of the initiation of highly active antiretroviral therapy (HAART), the absolute production rates of circulating T cells increased, and normal half-lives and production rates were restored by 12-36 months. Interpatient heterogeneity in the absolute degree of turnover correlated with the relative proportion of naive- and memory/effector-phenotype T cells in each of the CD4+ and CD8+ populations. The half-lives of naive-phenotype T cells ranged from 116-365 days (fractional replacement rates of 0.19-0.60% per day), whereas memory/effector-phenotype T cells persisted with half-lives from 22-79 days (fractional replacement rates of 0.87-3.14% per day). Naive-phenotype T cells were more abundant, and the half-life of total T cells was prolonged in individuals with abundant thymic tissue, as assessed by computed tomography. Such interpatient variation in T-cell kinetics may be reflective of differences in functional immune reconstitution after treatment for HIV-1 disease.

AB - HIV-1 disease is associated with pathological effects on T-cell production, destruction, and distribution. Using the deuterated (2H) glucose method for endogenous labeling, we have analyzed host factors that influence T-cell turnover in HIV-1-uninfected and -infected humans. In untreated HIV-1 disease, the average half life of circulating T cells was diminished without compensatory increases in cell production. Within 12 weeks of the initiation of highly active antiretroviral therapy (HAART), the absolute production rates of circulating T cells increased, and normal half-lives and production rates were restored by 12-36 months. Interpatient heterogeneity in the absolute degree of turnover correlated with the relative proportion of naive- and memory/effector-phenotype T cells in each of the CD4+ and CD8+ populations. The half-lives of naive-phenotype T cells ranged from 116-365 days (fractional replacement rates of 0.19-0.60% per day), whereas memory/effector-phenotype T cells persisted with half-lives from 22-79 days (fractional replacement rates of 0.87-3.14% per day). Naive-phenotype T cells were more abundant, and the half-life of total T cells was prolonged in individuals with abundant thymic tissue, as assessed by computed tomography. Such interpatient variation in T-cell kinetics may be reflective of differences in functional immune reconstitution after treatment for HIV-1 disease.

UR - http://www.scopus.com/inward/record.url?scp=0034060982&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034060982&partnerID=8YFLogxK

M3 - Article

C2 - 10712441

AN - SCOPUS:0034060982

VL - 105

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 5

ER -