HIV-induced abnormalities in myelopoiesis and their recovery following antiretroviral therapy.
HIV-1 infection is associated with hematologic abnormalities including defective myelopoiesis. Most studies of myelopoiesis during HIV-1 infection were performed using unfractionated bone marrow-derived mononuclear cells, thus resulting in significant inter-individual variability in the numbers of cultured precursors. Here we evaluated the myelopoietic potential of circulating CD34+ progenitors by conducting a longitudinal analysis of antiretroviral therapy (ART)-induced changes of colony forming units-granulocyte and monocyte (CFU-GM) growth. Twelve HIV-infected individuals were studied longitudinally before and after initiation of ART (i.e. at a time when plasma HIV-RNA levels had become undetectable); thirty-one HIV-uninfected healthy individuals were enrolled as controls. Peripheral blood-derived CD34+ progenitors were purified by immunomagnetic sorting, and cultured in methylcellulose-based medium containing stem cell factor, granulocyte-monocyte colony-stimulating factor and interleukin-3. ART-induced changes in the proportion of CD8+ T cells expressing surface HLA-DR were also evaluated. We found that CFU-GM levels were increased in untreated HIV-infected individuals when compared to uninfected controls but declined significantly following ART, in parallel with the decline of HIV-RNA levels in plasma and with the down-regulation of HLA-DR expression on CD8+ T cells. These findings suggest that, in untreated HIV-infected individuals, chronic inflammation and/or immune activation is associated with defective myelopoiesis and accumulation of myeloid precursors. ART-induced suppression of HIV-1 replication is associated with normalization of CFU-GM levels.
Costantini
Andrea
A
Dipartimento di Scienze Mediche e Chirurgiche, Università Politecnica delle Marche, Ancona, Italy. a.costantini@univpm.it
Giuliodoro
Simona
S
Butini
Luca
L
Silvestri
Guido
G
Leoni
Pietro
P
Montroni
Maria
M
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D023241:Antiretroviral Therapy, Highly Active; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D005260:Female; D006098:Granulocytes / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D023461:Myeloid Progenitor Cells / Q000737:chemistry / Q000502:physiology*; D013234:Stem Cells
D018952:Antigens, CD34; D003470:Culture Media