Depletion of CD34+ CD4+ cells in bone marrow from HIV-1-infected individuals.
Pancytopenia as a consequence of bone marrow abnormalities is commonly seen in HIV-infected individuals. To examine the effect that HIV-1 has on hematopoietic cells, we compared hematopoietic properties of bone marrow samples from HTV+ patients at various stages of disease with bone marrow samples from uninfected donors. While the absolute number of recovered CD34+ cells and the cloning efficiency of these cells did not differ significantly in HIV+ donors, the percentage of CD34+ CD4+ cells was significantly depleted in late-stage HIV+ patients. We observed a direct correlation between the numbers of CD34+ CD4+ cells in the bone marrow and the peripheral CD4 count. Further characterization of the CD34+ CD4+ subpopulation demonstrated that these cells expressed lower levels of HLA-DR on their surface compared with CD34+ CD4- cells, suggesting an immature phenotype. We also found evidence for expression of HIV-1 coreceptors CXCR-4 and CKR-5 message and protein in CD34+ bone marrow cells. While this finding suggested that hematopoietic cells might be susceptible to HIV infection at an early stage of maturation, thus affecting different cell lineages as they matured, we did not find any evidence for infection of HIV in these cells. These data suggest that HIV affects early hematopoietic progenitor cells either directly or indirectly, and in particular CD34+ CD4+ cells. This finding has important implications for disease pathogenesis and for application of gene therapy approaches that use CD34+ hematopoietic cells.
Banda
N K
NK
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA. nirmal.banda@uchsc.edu
Simon
G R
GR
Sipple
J D
JD
Terrell
K L
KL
Archer
P
P
Shpall
E J
EJ
Akkina
R K
RK
Myers
A M
AM
Harrison
G S
GS
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis*; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015704:CD4 Antigens / Q000032:analysis*; D002999:Clone Cells; D015658:HIV Infections / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D008875:Middle Aged; D010198:Pancytopenia / Q000276:immunology*; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis
D018952:Antigens, CD34; D015704:CD4 Antigens; D006684:HLA-DR Antigens; D019713:Receptors, CCR5; D019718:Receptors, CXCR4