Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–infected Individuals before and after Effective Therapy

doi:10.1084/jem.190.5.725

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© The Rockefeller University Press, 0022-1007/1999/9/725/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 5, September 6, 1999 725-732

Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–infected Individuals before and after Effective Therapy

Linqi Zhang^a, Sharon R. Lewin^a, Martin Markowitz^a, Hsi-Hsun Lin^a, Eva Skulsky^a, Rose Karanicolas^a, Yuxian He^a, Xia Jin^a, Sarah Tuttleton^a, Mika Vesanen^a, Hans Spiegel^a, Rhonda Kost^a, Jan van Lunzen^b, Hans-Juergen Stellbrink^b, Steven Wolinsky^c, William Borkowsky^d, Paul Palumbo^e, Leondios G. Kostrikis^a, and David D. Ho^a
^a From the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
^b University Hospital Eppendorf, 20246 Hamburg, Germany
^c Department of Medicine, Northwestern University School of Medicine, Chicago, Illinois 60611
^d Department of Pediatrics, New York University Medical Center, New York, New York 10016
^e Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103

Correspondence to: David D. Ho, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave., New York, NY 10016. Tel:212-448-5000 Fax:212-725-1126 E-mail:dho{at}adarc.org.

The role of the thymus in HIV-1 pathogenesis remains unclear.We developed an assay to quantify the number of recent thymicemigrants in blood based on the detection of a major excisionalDNA byproduct (termed ${alpha}$ 1 circle) of T cell receptor rearrangement.By studying 532 normal individuals, we found that ${alpha}$ 1 circle numbersin blood remain high for the first 10–15 yr of life, asharp drop is seen in the late teen years, and a gradual declineoccurs thereafter. Compared with age-matched uninfected controlindividuals, ${alpha}$ 1 circle numbers in HIV-1–infected adultswere significantly reduced; however, there were many individualswith normal ${alpha}$ 1 circle numbers. In 74 individuals receiving highlyactive antiretroviral therapy, we found no appreciable effecton ${alpha}$ 1 circle numbers in those whose baseline values were alreadywithin the normal range, but significant increases were observedin those with a preexisting impairment. The increases in ${alpha}$ 1 circlenumbers were, however, numerically insufficient to account forthe rise in levels of naive T lymphocytes. Overall, it is difficultto invoke thymic regenerative failure as a generalized mechanismfor CD4 lymphocyte depletion in HIV-1 infection, as ${alpha}$ 1 circlenumbers are normal in a substantial subset of HIV-1–infectedindividuals.

Key Words: HIV, thymus gland, aging, pathogenesis, drug therapy

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