title: Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy.
abstract: The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed alpha1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that alpha1 circle numbers in blood remain high for the first 10-15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, alpha1 circle numbers in HIV-1-infected adults were significantly reduced; however, there were many individuals with normal alpha1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on alpha1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in alpha1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as alpha1 circle numbers are normal in a substantial subset of HIV-1-infected individuals.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: S R
authors.initials: SR
authors.lastname: Lewin
authors.forename: M
authors.initials: M
authors.lastname: Markowitz
authors.forename: H H
authors.initials: HH
authors.lastname: Lin
authors.forename: E
authors.initials: E
authors.lastname: Skulsky
authors.forename: R
authors.initials: R
authors.lastname: Karanicolas
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.forename: X
authors.initials: X
authors.lastname: Jin
authors.forename: S
authors.initials: S
authors.lastname: Tuttleton
authors.forename: M
authors.initials: M
authors.lastname: Vesanen
authors.forename: H
authors.initials: H
authors.lastname: Spiegel
authors.forename: R
authors.initials: R
authors.lastname: Kost
authors.forename: J
authors.initials: J
authors.lastname: van Lunzen
authors.forename: H J
authors.initials: HJ
authors.lastname: Stellbrink
authors.forename: S
authors.initials: S
authors.lastname: Wolinsky
authors.forename: W
authors.initials: W
authors.lastname: Borkowsky
authors.forename: P
authors.initials: P
authors.lastname: Palumbo
authors.forename: L G
authors.initials: LG
authors.lastname: Kostrikis
authors.forename: D D
authors.initials: DD
authors.lastname: Ho
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000097:blood / Q000235:genetics / Q000276:immunology; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001483:Base Sequence; D016022:Case-Control Studies; D002465:Cell Movement; D002648:Child; D017931:DNA Primers / Q000235:genetics; D004270:DNA, Circular / Q000097:blood / Q000235:genetics; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D017931:DNA Primers; D004270:DNA, Circular