Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy

Linqi Zhang, Sharon R. Lewin, Martin Markowitz, Hsi Hsun Lin, Eva Skulsky, Rose Karanicolas, He Yuxian, Jin Xia, Sarah Tuttleton, Mika Vesanen, Hans Spiegel, Rhonda Kost, Jan Van Lunzen, Hans Juergen Stellbrink, Steven Wolinsky, William Borkowsky, Paul Palumbo, Leondios G. Kostrikis, David D. Ho*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

307 Scopus citations

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 α1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that α1 circle numbers in blood remain high for the first 1015 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, α1 circle numbers in HIV-1-infected adults were significantly reduced; however, there were many individuals with normal α1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on α1 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 α1 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 α1 circle numbers are normal in a substantial subset of HIV-1- infected individuals.

Original languageEnglish (US)
Pages (from-to)725-732
Number of pages8
JournalJournal of Experimental Medicine
Volume190
Issue number5
DOIs
StatePublished - Sep 6 1999

Keywords

  • Aging
  • Drug therapy
  • HIV
  • Pathogenesis
  • Thymus gland

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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