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Blood, 15 July 2004, Vol. 104, No. 2, pp. 470-477.
Prepublished online as a Blood First Edition Paper on April 1, 2004; DOI 10.1182/blood-2003-12-4265.
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Submitted December 15, 2003
Accepted March 11, 2004
De novo T cell generation at different ages and stages of HIV-1 disease
Massimo Nobile, Rafael Correa, Jose A Borghans, Philippe Schneider, Rob J de Boer, and Giuseppe Pantaleo*
Division of Immunology and Allergy, CHUV, Lausanne, Switzerland
Division of Immunology and Allergy, CHUV, Lausanne, Switzerland; Laboratory of Molecular Immuno-Biology, HGUGM, Madrid, Spain
Department of Clinical Viro-Immunology, University of Amsterdam, Amsterdam, The Netherlands
Service Regional Vaudois de Transfusion Sanguine, Lausanne, Switzerland
Theoretical Biology, Utrecht University, Utrecht, The Netherlands
* Corresponding author; email: Giuseppe.Pantaleo{at}chuv.hospvd.ch.
De novo T cell generation was assessed by the determination of T cell receptor excision circles (TRECs) at different ages and stages of HIV-1 infection. TRECs were measured in purified CD4 and CD8 T cells of a large cohort of HIV-1 infected subjects (n=297) with chronic infection and no previous antiretroviral treatment and in a control group (n=120) of HIV-negative subjects. HIV-1 infected subjects were stratified on the basis of CD4 T cell counts in three groups: a) early stage disease (>500 CD4 T cells); b) intermediate stage (<500 >200 cells); and c) late stage (<200 cells). As compared to the control group, CD8 TREC contents were severely reduced (P<0.001) in HIV-1 infected subjects regardless of the stage of HIV disease. In contrast, CD4 TREC contents were significantly increased (P=0.003) in HIV-1 infected subjects at early stage disease, similar at intermediate stage disease, and severely reduced only at late stage disease. We show that the increase in CD4 TRECs was mostly limited to younger (<44 years) patients at early stage disease. Our results demonstrate a dichotomy between TREC contents in CD4 and CD8 T cell populations in HIV-1 infection and indicate that thymus function in younger subjects is preserved at early and intermediate stages of HIV infection.
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