title: Telomere length, telomerase activity, and replicative potential in HIV infection: analysis of CD4+ and CD8+ T cells from HIV-discordant monozygotic twins.
abstract: To address the possible role of replicative senescence in human immunodeficiency virus (HIV) infection, telomere length, telomerase activity, and in vitro replicative capacity were assessed in peripheral blood T cells from HIV+ and HIV- donors. Genetic and age-specific effects on these parameters were controlled by studying HIV-discordant pairs of monozygotic twins. Telomere terminal restriction fragment (TRF) lengths from CD4+ T cells of HIV+ donors were significantly greater than those from HIV- twins. In contrast, telomere lengths in CD8+ T cells from HIV+ donors were shorter than in HIV- donors. The in vitro replicative capacity of CD4+ cells from HIV+ donors was equivalent to that of HIV- donors in response to stimulation through T cell receptor CD3 and CD28. Little or no telomerase activity was detected in freshly isolated CD4+ or CD8+ lymphocytes from HIV+ or HIV- donors, but was induced by in vitro stimulation of both HIV+ and HIV- donor cells. These results suggest that HIV infection is associated with alterations in the population dynamics of both CD4+ and CD8+ T cells, but fail to provide evidence for clonal exhaustion or replicative senescence as a mechanism underlying the decline in CD4+ T cells of HIV-infected donors.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Palmer
authors.forename: N
authors.initials: N
authors.lastname: Weng
authors.forename: B L
authors.initials: BL
authors.lastname: Levine
authors.forename: C H
authors.initials: CH
authors.lastname: June
authors.forename: H C
authors.initials: HC
authors.lastname: Lane
authors.forename: R J
authors.initials: RJ
authors.lastname: Hodes
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016922:Cellular Senescence; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D019098:Telomerase / Q000032:analysis*; D016615:Telomere / Q000648:ultrastructure*; D014430:Twins, Monozygotic
chemical_list: D019098:Telomerase