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Article
Nature Medicine  6, 1036 - 1042 (2000)
doi:10.1038/79549

Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection

Mette D. Hazenberg1, Sigrid A. Otto1, James W.T. Cohen Stuart2, 3, Martie C.M. Verschuren4, Jan C.C. Borleffs2, Charles A.B. Boucher3, Roel A. Coutinho5, Joep M.A. Lange6, Tobias F. Rinke de Wit7, Aster Tsegaye7, Jacques J.M. van Dongen4, Dörte Hamann1, Rob J. de Boer8 & Frank Miedema1, 9

1  Department of Clinical Viro-Immunology, CLB, and the Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066CX, Amsterdam, The Netherlands

2  Department of Internal Medicine, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

3  Department of Virology, Eijkman-Winkler Institute, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

4  Department of Immunology, Erasmus University, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands

5  Department of Public Health and Environment, Municipal Health Service, P.O. Box 2200, 1000 CE, Amsterdam, The Netherlands

6  Division of Infectious Diseases, Tropical medicine and AIDS and the National AIDS Therapy Evaluation Center (NATEC), Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, The Netherlands,

7  Ethiopian-Netherlands AIDS Research Project (ENARP) at the Ethiopian Health and Nutrition Research Institute (EHNRI), P.O. Box 1242, Addis Ababa, Ethiopia

8  Theoretical Biology, Utrecht University, Padualaan 8, 3584 CH, The Netherlands,

9  Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Correspondence should be addressed to Frank Miedema F_Miedema@CLB.nl
Recent thymic emigrants can be identified by T cell receptor excision circles (TRECs) formed during T-cell receptor rearrangement. Decreasing numbers of TRECs have been observed with aging and in human immunodeficiency virus (HIV)-1 infected individuals, suggesting thymic impairment. Here, we show that in healthy individuals, declining thymic output will affect the TREC content only when accompanied by naive T-cell division. The rapid decline in TRECs observed during HIV-1 infection and the increase following HAART are better explained not by thymic impairment, but by changes in peripheral T-cell division rates. Our data indicate that TREC content in healthy individuals is only indirectly related to thymic output, and in HIV-1 infection is mainly affected by immune activation.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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