title: Quantification of naive and memory T-cell turnover during HIV-1 infection.
abstract: BACKGROUND
  In HIV infection, the homeostasis of CD4 and CD8 T cells is dramatically disturbed, and several studies have pointed out that T-cell turnover rates are increased. To understand how the CD4 and CD8 T-cell pools are affected, it is important to have quantitative insights into the lifespans of the cells constituting the different T-lymphocyte populations.
  
  
  METHODS
  We used long-term in-vivo H2O labeling and mathematical modeling to estimate the average lifespans of naive and memory CD4 and CD8 T cells in untreated (n = 4) and combination antiretroviral therapy-treated (n = 3) HIV-1-infected individuals.
  
  
  RESULTS
  During untreated chronic HIV-1 infection, naive CD4 and CD8 T cells lived on average 618 and 271 days, whereas memory CD4 and CD8 T cells had average lifespans of 53 and 43 days, respectively. These lifespans were at least three-fold shorter than those in healthy controls (n = 5). In patients on effective combination antiretroviral therapy with total CD4 T-cell counts in the normal range, we found that naive CD4 and CD8 T-cell lifespans had not completely normalized and were still two-fold shortened.
  
  
  CONCLUSIONS
  The average lifespan of both naive and memory CD4 and CD8 T cells decreased during untreated chronic HIV-1 infection. Although the turnover of the memory T-cell populations nearly normalized during effective treatment, the turnover of naive CD4 and CD8 T cells did not seem to normalize completely.
authors.affiliation: aLaboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht bTheoretical Biology and Bioinformatics, Utrecht University, Utrecht cDepartment of Gastroenterology and Hepatology, Erasmus MC Rotterdam, Rotterdam, The Netherlands dDepartment of Infectious Disease Epidemiology, Imperial College, London, UK eDepartment of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht fDepartment of Internal Medicine and Gastroenterology, Kennemer Gasthuis, Haarlem gDepartment of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center hIATEC, Academic Medical Center iDepartment of Internal Medicine, Academic Medical Center jDepartment of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands. *Nienke Vrisekoop, Julia Drylewicz, Rogier Van Gent contributed equally to this study; Rob J. de Boer, Kiki Tesselaar, José A.M. Borghans also contributed equally to this study.
authors.forename: Nienke
authors.initials: N
authors.lastname: Vrisekoop
authors.forename: Julia
authors.initials: J
authors.lastname: Drylewicz
authors.forename: Rogier
authors.initials: R
authors.lastname: Van Gent
authors.forename: Tendai
authors.initials: T
authors.lastname: Mugwagwa
authors.forename: Steven F L
authors.initials: SF
authors.lastname: Van Lelyveld
authors.forename: Ellen
authors.initials: E
authors.lastname: Veel
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Otto
authors.forename: Mariëtte T
authors.initials: MT
authors.lastname: Ackermans
authors.forename: Joost N
authors.initials: JN
authors.lastname: Vermeulen
authors.forename: Hidde H
authors.initials: HH
authors.lastname: Huidekoper
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Boer
authors.forename: Kiki
authors.initials: K
authors.lastname: Tesselaar
authors.forename: José A M
authors.initials: JA
authors.lastname: Borghans
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007156:Immunologic Memory; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents