title: Impact of HIV-1 infection and highly active antiretroviral therapy on the kinetics of CD4+ and CD8+ T cell turnover in HIV-infected patients.
abstract: To evaluate the effects of HIV infection on T cell turnover, we examined levels of DNA synthesis in lymph node and peripheral blood mononuclear cell subsets by using ex vivo labeling with BrdUrd. Compared with healthy controls (n = 67), HIV-infected patients (n = 57) had significant increases in the number and fraction of dividing CD4(+) and CD8(+) T cells. Higher percentages of dividing CD4(+) and CD8(+) T cells were noted in patients with the higher viral burdens. No direct correlation was noted between rates of T cell turnover and CD4(+) T cell counts. Marked reductions in CD4(+) and CD8(+) T cell proliferation were seen in 11/11 patients 1-12 weeks after initiation of highly active antiretroviral therapy (HAART). These reductions persisted for the length of the study (16-72 weeks). Decreases in naive T cell proliferation correlated with increases in the levels of T cell receptor rearrangement excision circles. Division of CD4(+) and CD8(+) T cells increased dramatically in association with rapid increases in HIV-1 viral loads in 9/9 patients 5 weeks after termination of HAART and declined to pre-HAART-termination levels 8 weeks after reinitiation of therapy. These data are consistent with the hypothesis that HIV-1 infection induces a viral burden-related, global activation of the immune system, leading to increases in lymphocyte proliferation.
authors.affiliation: Science Applications International Corporation-Frederick, Clinical Services Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: J A
authors.initials: JA
authors.lastname: Kovacs
authors.forename: M W
authors.initials: MW
authors.lastname: Baseler
authors.forename: J W
authors.initials: JW
authors.lastname: Adelsberger
authors.forename: R L
authors.initials: RL
authors.lastname: Dewar
authors.forename: V
authors.initials: V
authors.lastname: Natarajan
authors.forename: M C
authors.initials: MC
authors.lastname: Bosche
authors.forename: J A
authors.initials: JA
authors.lastname: Metcalf
authors.forename: R A
authors.initials: RA
authors.lastname: Stevens
authors.forename: L A
authors.initials: LA
authors.lastname: Lambert
authors.forename: W G
authors.initials: WG
authors.lastname: Alvord
authors.forename: M A
authors.initials: MA
authors.lastname: Polis
authors.forename: R T
authors.initials: RT
authors.lastname: Davey
authors.forename: D S
authors.initials: DS
authors.lastname: Dimitrov
authors.forename: H C
authors.initials: HC
authors.lastname: Lane
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens