The Journal of Experimental Medicine
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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

Original Article

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

Linqi Zhanga, Sharon R. Lewina, Martin Markowitza, Hsi-Hsun Lina, Eva Skulskya, Rose Karanicolasa, Yuxian Hea, Xia Jina, Sarah Tuttletona, Mika Vesanena, Hans Spiegela, Rhonda Kosta, Jan van Lunzenb, Hans-Juergen Stellbrinkb, Steven Wolinskyc, William Borkowskyd, Paul Palumboe, Leondios G. Kostrikisa, and David D. Hoa

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
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave., New York, NY 10016.212-725-1126212-448-5000

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 thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed {alpha}1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that {alpha}1 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, {alpha}1 circle numbers in HIV-1–infected adults were significantly reduced; however, there were many individuals with normal {alpha}1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on {alpha}1 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 {alpha}1 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 {alpha}1 circle numbers are normal in a substantial subset of HIV-1–infected individuals.

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

1used in this paper: HAART, highly active antiviral therapy; RTEs, recent thymic emigrants; SI, syncytium-inducing; TRECs, TCR excisional circles

L. Zhang and S.R. Lewin contributed equally to this work.

© 1999 The Rockefeller University Press


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