Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy
-
- Linqi Zhang
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Sharon R. Lewin
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Martin Markowitz
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Hsi-Hsun Lin
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Eva Skulsky
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Rose Karanicolas
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Yuxian He
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Xia Jin
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Sarah Tuttleton
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Mika Vesanen
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Hans Spiegel
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Rhonda Kost
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- Jan van Lunzen
- bUniversity Hospital Eppendorf, 20246 Hamburg, Germany
-
- Hans-Juergen Stellbrink
- bUniversity Hospital Eppendorf, 20246 Hamburg, Germany
-
- Steven Wolinsky
- cDepartment of Medicine, Northwestern University School of Medicine, Chicago, Illinois 60611
-
- William Borkowsky
- dDepartment of Pediatrics, New York University Medical Center, New York, New York 10016
-
- Paul Palumbo
- eDepartment of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103
-
- Leondios G. Kostrikis
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
-
- David D. Ho
- aFrom the Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016
説明
<jats:p>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 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, 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.</jats:p>
収録刊行物
-
- The Journal of Experimental Medicine
-
The Journal of Experimental Medicine 190 (5), 725-732, 1999-09-06
Rockefeller University Press