Impact of bone marrow hematopoiesis failure on T-cell generation during pathogenic simian immunodeficiency virus infection in macaques.
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.
Thiebot
Hugues
H
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, France.
Vaslin
Bruno
B
Derdouch
Sonia
S
Bertho
Jean-Marc
JM
Mouthon
Franck
F
Prost
Stéphane
S
Gras
Gabriel
G
Ducouret
Pierre
P
Dormont
Dominique
D
Le Grand
Roger
R
D000818:Animals; D017304:Annexin A5 / Q000097:blood; D018952:Antigens, CD34; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology; D016193:G1 Phase; D005786:Gene Expression Regulation; D019254:Genes, bcl-2; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000821:virology; D006706:Homeostasis; D038041:Lymphopoiesis; D008252:Macaca fascicularis / Q000097:blood* / Q000821:virology; D008297:Male; D008992:Monkey Diseases / Q000097:blood* / Q000473:pathology / Q000821:virology; D038042:Myelopoiesis; D016192:Resting Phase, Cell Cycle; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000473:pathology; D015302:Simian Immunodeficiency Virus; D019562:Viral Load
D017304:Annexin A5; D018952:Antigens, CD34