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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.
Submitted January 13, 2004
Service de Neurovirolgie, Centre de Recherches du Service de Sante des Armees, Commissariat a l'Energie Atomique (CEA), Laboratoire d'Immuno-Pathologie Experimentale, Fontenay-aux-Roses, France; Ecole Pratique des Hautes Etudes, Paris, France; Institut Paris-Sud sur les Cytokines, Universite Paris XI, Fontenay-aux-Roses, France * Corresponding author; email: legrand{at}dsvidf.cea.fr.
Experimental infection of macaques with pathogenic strains of simian immunodeficiency virus (SIV) represents one of the most relevant animal models for study human immunodeficiency virus (HIV) pathogenesis. In this study, we demonstrated a significant decrease in the generation of CD4+ T cells from bone marrow CD34+ progenitors in macaques infected with SIVmac251. This decrease appears to result from changes in the clonogenic potential of bone marrow 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-IC). Hematopoietic failure occurred as early as primary infection, in the absence of CD34+ bone marrow (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, although apoptosis markers appeared lowered, but a significantly higher that normal proportion of cells were in the G0/G1. This is the first demonstration that bone marrow hematopoiesis failure 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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