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Exposure of human CD34+ cells to human immunodeficiency virus type 1 does
not influence their expansion and proliferation of hematopoietic
progenitors in vitro
S Kaushal, VF La Russa, S Gartner, S Kessler, S Perfetto, Z Yu, DW Ritchey, J Xu, P Perera, J Kim, T Reid, DL Mayers, D St. Louis and JD Mosca
Department of Hematology and Vascular Biology, Walter Reed Army Institute
of Research, Washington, DC; USA.
The susceptibility of highly purified human CD34+ cells to monocytotropic
(Ba-L) and lymphotropic (A018-post) strains of human immunodeficiency
virus-1 (HIV-1) was examined. Liquid cultures initiated with fresh
immunomagnetically purified CD34+ cells using the K6.1 CD34 monoclonal
antibody (MoAb) (K6.1/CD34+) were positive for HIV expression 2 weeks after
exposure to HIV-1 Ba-L. These cells were initially greater than 90% CD34+
and had undetectable monocyte contamination by flow-cytometric staining and
side-scatter analyses, respectively, and undetectable T-cell contamination
by CD3 polymerase chain reaction (PCR) analysis. However, secondary CD34+
liquid cultures reselected from the primary liquid cultures 24 hours after
HIV exposure by panning with the ICH3 CD34 MoAb (ICH3/CD34+) and maintained
for an additional 14 days were negative for HIV expression. The
ICH3-unbound cells were positive for both spliced and unspliced HIV RNA
when exposed to HIV-1 Ba-L, and were DNA PCR positive when exposed to
either monocytotropic or lymphotropic HIV-1. To further test that CD34+
cells were not infectible by HIV-1, we exposed K6.1/CD34+ cells
continuously to HIV-1 in a culture system capable of maintaining and
expanding primitive CD34+ cells. HIV-exposed K6.1/CD34+ cells proliferated
and expanded as efficiently as uninfected cultures. However, when
reselected magnetically using the K6.1 CD34 MoAb after expansion for 7
days, bound K6.1/CD34+ cells were again negative for HIV-1 expression,
whereas unbound cells were positive for HIV-1 expression. These findings
suggest that a sequential CD34+ cell-selection process, in which the two
selections are separated by a brief culture period, can yield a population
of CD34+ cells that are not infected with HIV-1. This process may be useful
in the design of stem or progenitor cell- based transplantation therapies
for HIV infection.
Volume 88,
Issue 1,
pp. 130-137,
07/01/1996
Copyright © 1996 by The American Society of Hematology

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