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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.
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Submitted September 15, 2006
Accepted November 20, 2006
Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection
Marie-Lise Dion, Rebeka Bordi, Joumana Zeidan, Robert Asaad, Mohammed-Rachid Boulassel, Jean-Pierre Routy, Micheal M. Lederman, Rafick-Pierre Sekaly*, and Remi Cheynier
Laboratoire d'Immunologie, Centre de recherche du CHUM, Hopital Saint Luc, Montreal, Quebec, Canada
Dept of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada
Case Western Reserve University Center for AIDS Research, Cleveland, OH, United States
Immunodeficiency Service & Division of Hematology, Royal Victoria Hospital, McGill University Health Center, McGill University, Montreal, Quebec, Canada
INSERM U743, CR-CHUM, Universite de Montreal, Montreal, Quebec, Canada
Laboratoire d'Immunologie, Departement de Microbiologie et Immunologie, Universite de Montreal, Montreal, Quebec, Canada
Unite des Virus Lents, Institut Pasteur, Paris, France
* Corresponding author; email: rafick-pierre.sekaly{at}umontreal.ca.
In chronic HIV infection, most untreated patients lose naive CD4+ and CD8+ T-cells while a minority preserves them despite persistent high viremia. While 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/ TREC 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, while 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, while 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.
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