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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2912-2920. Prepublished online as a Blood First Edition Paper on December 12, 2006; DOI 10.1182/blood-2006-09-047308. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-09-047308v1 109/7/2912    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dion, M.-L. Articles by Cheynier, R. Search for Related Content PubMed PubMed Citation Articles by Dion, M.-L. Articles by Cheynier, R. Related Collections Immunobiology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection Marie-Lise Dion1,2, Rebeka Bordi1, Joumana Zeidan1,2, Robert Asaad3, Mohammed-Rachid Boulassel4, Jean-Pierre Routy4,5, Micheal M. Lederman3, Rafick-Pierre Sekaly1,2,5,6, and Remi Cheynier7 1 Laboratoire d'Immunologie, Centre de Recherches du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Hôpital Saint Luc, Montreal, QC, Canada; 2 Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada; 3 Case Western Reserve University Center for AIDS Research, Cleveland, OH; 4 Immunodeficiency Service and Division of Hematology, Royal Victoria Hospital, McGill University Health Centre, McGill University, Montreal, QC, Canada; 5 Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 743, CR-CHUM, Université de Montréal, QC, Canada; 6 Laboratoire d'Immunologie, Département de Microbiologie et Immunologie, Université de Montréal, QC, Canada; 7 Unité des Virus Lents, Institut Pasteur, Paris, France In chronic HIV infection, most untreated patients lose naive CD4+ and CD8+ T cells, whereas a minority preserve them despite persistent high viremia. Although antiretroviral therapy (ART)–mediated viral suppression generally results in a rise of naive and total CD4+ T cells, certain patients experience very little or no T-cell reconstitution. High peripheral T-cell activation has been linked to poor clinical outcomes, interfering with previous evaluations of thymic function in disease progression and therapy-mediated T-cell recovery. To circumvent this, we used the sj/ßTREC ratio, a robust index of thymopoiesis that is independent of peripheral T-cell proliferation, to evaluate the thymic contribution to the preservation and restoration of naive CD4+ T cells. We show that the loss of naive and total CD4+ T cells is the result of or is exacerbated by a sustained thymic defect, whereas efficient thymopoiesis supports naive and total CD4+ T-cell maintenance in slow progressor patients. In ART-treated patients, CD4+ T-cell recovery was associated with the normalization of thymopoiesis, whereas the thymic defect persisted in aviremic patients who failed to recover CD4+ T-cell counts. Overall, we demonstrate that efficient thymopoiesis is key in the natural maintenance and in therapy-mediated recovery of naive and total CD4+ T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Vrisekoop, R. van Gent, A. B. de Boer, S. A. Otto, J. C. C. Borleffs, R. Steingrover, J. M. Prins, T. W. Kuijpers, T. F. W. Wolfs, S. P. M. Geelen, et al. Restoration of the CD4 T Cell Compartment after Long-Term Highly Active Antiretroviral Therapy without Phenotypical Signs of Accelerated Immunological Aging J. Immunol., July 15, 2008; 181(2): 1573 - 1581. [Abstract] [Full Text] [PDF] S. N. Gordon, R. M. Dunham, J. C. Engram, J. Estes, Z. Wang, N. R. Klatt, M. Paiardini, I. V. Pandrea, C. Apetrei, D. L. Sodora, et al. Short-Lived Infected Cells Support Virus Replication in Sooty Mangabeys Naturally Infected with Simian Immunodeficiency Virus: Implications for AIDS Pathogenesis J. Virol., April 1, 2008; 82(7): 3725 - 3735. [Abstract] [Full Text] [PDF] E. Castermans, F. Baron, E. Willems, N. Schaaf-Lafontaine, N. Meuris, A. Gothot, J.-F. Vanbellighen, C. Herens, L. Seidel, V. Geenen, et al. Evidence for neo-generation of T cells by the thymus after non-myeloablative conditioning Haematologica, February 1, 2008; 93(2): 240 - 247. [Abstract] [Full Text] [PDF] I. Karlsson, B. Malleret, P. Brochard, B. Delache, J. Calvo, R. Le Grand, and B. Vaslin Dynamics of T-Cell Responses and Memory T Cells during Primary Simian Immunodeficiency Virus Infection in Cynomolgus Macaques J. Virol., December 15, 2007; 81(24): 13456 - 13468. [Abstract] [Full Text] [PDF] D. Gautier, S. Beq, C. S. Cortesao, A. E. Sousa, and R. Cheynier Efficient Thymopoiesis Contributes to the Maintenance of Peripheral CD4 T Cells during Chronic Human Immunodeficiency Virus Type 2 Infection J. Virol., November 15, 2007; 81(22): 12685 - 12688. [Abstract] [Full Text] [PDF]

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