title: T-cell division in human immunodeficiency virus (HIV)-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART).
abstract: In human immunodeficiency virus (HIV)-1 infection, highly increased T-cell turnover was proposed to cause exhaustion of lymphocyte production and consequently development of AIDS. Here, we investigated cell proliferation, as measured by expression of the Ki-67 nuclear antigen, in peripheral blood CD4(+) and CD8(+) lymphocyte subpopulations before and during highly active antiretroviral therapy (HAART). In untreated HIV-1 infection, both the percentage and number of Ki-67(+) CD4(+) and CD8(+) lymphocytes were significantly increased, compared with values obtained from healthy individuals. A more than 10-fold increase in the percentage of dividing naive CD4(+) T cells in the blood was found when the number of these cells were below 100 per microL. HAART induced an immediate decline in Ki-67 antigen expression, despite often very low CD4(+) T-cell numbers, arguing against increased proliferation being a homeostatic response. After approximately 24 weeks of HAART treatment, a transient increase in the number of proliferating cells was seen, but only in the CD4(+) CD27(+) memory pool. In the CD8(+) T-cell compartment, the number of dividing cells was elevated 20- to 25-fold. This increase was most notable in the CD27(+) CD 45RO(+) and CD27(-) CD45RO(+) memory CD8(+) T-cell pool, corresponding with the degree of expansion of these subsets. Reduction of plasma HIV-RNA load by HAART was accompanied by a decrease in numbers and percentages of dividing cells in all CD8(+) T-cell subsets. Taken together, our results indicate that peripheral T-cell proliferation is a consequence of generalized immune activation. (Blood. 2000;95:249-255)
authors.affiliation: Department of Clinical Viro-Immunology, CLB, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M D
authors.initials: MD
authors.lastname: Hazenberg
authors.forename: J W
authors.initials: JW
authors.lastname: Stuart
authors.forename: S A
authors.initials: SA
authors.lastname: Otto
authors.forename: J C
authors.initials: JC
authors.lastname: Borleffs
authors.forename: C A
authors.initials: CA
authors.lastname: Boucher
authors.forename: R J
authors.initials: RJ
authors.lastname: de Boer
authors.forename: F
authors.initials: F
authors.lastname: Miedema
authors.forename: D
authors.initials: D
authors.lastname: Hamann
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D019394:Ki-67 Antigen / Q000276:immunology; D019259:Lamivudine / Q000627:therapeutic use; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D012367:RNA, Viral / Q000097:blood; D019258:Saquinavir / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D019394:Ki-67 Antigen; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D019258:Saquinavir