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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.
IMMUNOBIOLOGY De novo T-cell generation in patients at different ages and stages of HIV-1 diseaseFrom the Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; Laboratory of Molecular Immuno-Biology, Hospital General Universitario Gregorio Marañón (HGUGM), Madrid, Spain; Department of Clinical Viro-Immunology, Sanquin Research at Centraal Laboratorium van de Bloedtransfusiedienst van het Nederlandse Rode Kruis (CLB) and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands; Service Régional Vaudois de Transfusion Sanguine, Lausanne, Switzerland; and Theoretical Biology, Utrecht University, The Netherlands.
We assessed de novo T-cell generation by determining T-cell receptor-rearrangement excision circles (TRECs) based on patient age and on stage 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 but no previous antiretroviral treatment and of a control group of HIV-negative subjects (n = 120). HIV-1-infected subjects were stratified on the basis of CD4 T-cell counts in 3 groups, early-stage disease (more than 500 CD4 T cells), intermediate-stage disease (200-500 CD4 T cells), and late-stage disease (fewer than 200 CD4 T cells). Compared with the control group, CD8 TREC contents were severely reduced (P < .001) in HIV-1-infected subjects regardless of the stage of HIV disease. In contrast, CD4 TREC contents were significantly increased (P = .003) in HIV-1-infected subjects during 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 (younger than 45 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. (Blood. 2004;104:470-477)
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