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Blood, 1 May 2002, Vol. 99, No. 9, pp. 3310-3318
IMMUNOBIOLOGY
Interleukin-7-treated naive T cells can be productively infected
by T-cell-adapted and primary isolates of human immunodeficiency
virus 1
Carolyn M. Steffens,
Elizabeth Z. Managlia,
Alan Landay, and
Lena Al-Harthi
From the Department of Immunology/Microbiology at
Rush-Presbyterian-St Luke's Medical Center, Rush University,
Chicago, IL.
Although human immunodeficiency virus (HIV)
gag/pol DNA can be detected in naive T cells,
whether naive T cells can be productively infected by HIV is still
questionable. Given that interleukin-7 (IL-7) is a prospective
therapeutic immunomodulator for the treatment of HIV, we
evaluated the effect of IL-7 on promoting naive T-cell infection
of laboratory-adapted (IIIB), M-tropic, and primary isolates of HIV.
Initially, we determined that the 3 cell surface markers widely used to
identify naive T cells (CD45RA+CD45RO ,
CD45RA+CD62L+, and
CD45RO CD27+CD95low) are all
equivalent in T-cell receptor excision circle content, a marker for the
replicative history of a cell as well as for de novo T cells. We
therefore used CD45RA+CD45RO expression to
define naive T cells in this study. We demonstrate that although
untreated or IL-2-treated naive T cells are not productively infected
by HIV, IL-7 pretreatment mediated the productive infection of
laboratory-adapted, M-tropic, and primary isolates of HIV as determined
by p24 core antigen production. This up-regulation was between 8- and
58-fold, depending on the HIV isolate used. IL-7 pretreatment of naive
T cells also potently up-regulated surface expression of CXCR4 but not
CCR5 and mediated the expansion of naive T cells without the
acquisition of the primed CD45RO phenotype. Collectively, these data
indicate that IL-7 augments naive T-cell susceptibility to HIV and that
under the appropriate environmental milieu, naive T cells may be a
source of HIV productive infection. This information needs to be
considered in evaluating IL-7 as an immunomodulator for HIV-infected patients.

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