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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2403-2409.
Prepublished online as a Blood First Edition Paper on September 23, 2004; DOI 10.1182/blood-2004-01-0025.


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IMMUNOBIOLOGY

Impact of bone marrow hematopoiesis failure on T-cell generation during pathogenic simian immunodeficiency virus infection in macaques

Hugues Thiebot, Bruno Vaslin, Sonia Derdouch, Jean-Marc Bertho, Franck Mouthon, Stéphane Prost, Gabriel Gras, Pierre Ducouret, Dominique Dormont, and Roger Le Grand

From the Commissariat à l'Energie Atomique (CEA), Laboratoire d'Immuno-Pathologie Expérimentale, Service de Neurovirologie, Centre de Recherches du Service de Santé des Armées, Ecole Pratique des Hautes Etudes, Institut Paris-Sud sur les Cytokines, Université Paris XI, Fontenay aux Roses, France; Institut de Recherche et de Sûreté Nucléaire, Fontenay aux Roses, France; and Université de Caen, Anestésiologie expérimentale et physiologie cellulaire, Caen, France.

Experimental infection of macaques with pathogenic strains of simian immunodeficiency virus (SIV) represents one of the most relevant animal models for studying HIV pathogenesis. In this study, we demonstrated a significant decrease in the generation of CD4+ T cells from bone marrow (BM) CD34+ progenitors in macaques infected with SIVmac251. This decrease appears to result from changes in the clonogenic potential of BM progenitors of both the myeloid and lymphoid lineages. We also demonstrated a significant decrease in the numbers of the most immature long-term culture-initiating cells (LTC-ICs). Hematopoietic failure occurred as early as primary infection, in the absence of CD34+ BM cell infection and was not related to plasma viral load. No major change was observed in the phenotype of BM CD34+ cells from infected macaques, including apoptosis markers such as annexin V staining and BcL-2 expression, but a significantly higher that normal proportion of cells were in the G0/G1 phase. This is the first demonstration that failure of BM hematopoiesis results in impaired T-cell production, which may contribute to the disruption of T-lymphocyte homeostasis characteristic of pathogenic lentiviral infections in primates.


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