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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

Nature Medicine volume 6, pages 1036–1042 (2000)Cite this article

Abstract

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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Figure 1: Correlation between TRECs and naive T-cell numbers.
Figure 2: The model behavior as a function of age (a, b and c).
Figure 3: The model behavior of an HIV-1 infected, 30-year old individual over a time period of one year.
Figure 4: In vivo dilution of TRECs.
Figure 5: Effect of HAART on TREC content.

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Acknowledgements

Patients and physicians are gratefully acknowledged for their participation in the studies. We thank Marja J. Willemse and Bas Dutilh for technical assistance, and Hanneke Schuitemaker and Rene van Lier for critical reading of the manuscript. This study was financially supported by the Dutch AIDS Foundation, the Netherlands Ministry of Foreign Affairs and the Ethiopian Ministry of Health (EHNRI-ENARP), Hoffman-La Roche, Bristol Myers Squibb and Dutch Cancer Society / Koningin Wilhelmina Fonds (grant EUR 95-1015; M.V. and J.vD.).

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Authors and Affiliations

  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

    Mette D. Hazenberg, Sigrid A. Otto, Dörte Hamann & Frank Miedema

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

    James W.T. Cohen Stuart & Jan C.C. Borleffs

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

    James W.T. Cohen Stuart & Charles A.B. Boucher

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

    Martie C.M. Verschuren & Jacques J.M. van Dongen

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

    Roel A. Coutinho

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

    Joep M.A. Lange

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

    Tobias F. Rinke de Wit & Aster Tsegaye

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

    Rob J. de Boer

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

    Frank Miedema

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Correspondence to Frank Miedema.

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Hazenberg, M., Otto, S., Stuart, J. et al. 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. Nat Med 6, 1036–1042 (2000). https://doi.org/10.1038/79549

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