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Blood, 15 July 2001, Vol. 98, No. 2, pp. 383-389
IMMUNOBIOLOGY
The HIV protease inhibitor Indinavir inhibits cell-cycle
progression in vitro in lymphocytes of HIV-infected and
uninfected individuals
Surendra Chavan,
Sangeetha Kodoth,
Rajendra Pahwa, and
Savita Pahwa
From the Division of Allergy/Immunology, Department of
Pediatrics, North Shore University Hospital, New York University School
of Medicine, Manhasset, NY.
Indinavir (IDV) is a potent and selective human immunodeficiency
virus type 1 (HIV-1) protease inhibitor (PI) widely used in
antiretroviral therapy for suppression of HIV, but its effects on the
immune system are relatively unknown. Recently, it has been reported
that PIs inhibit lymphocyte apoptosis. In the present study we have
investigated the effects of ex vivo addition of IDV on lymphocyte
activation and apoptosis in cells from HIV-infected children (n = 18)
and from healthy uninfected individuals (controls, n = 5) as well as
in Jurkat and PM1 T-cell lines. Pretreatment of control peripheral
blood mononuclear cell (PBMC) cultures with IDV resulted in a
dose-dependent inhibition of lymphoproliferative responses to different
activation stimuli. Additionally, this treatment led to cell-cycle
arrest in G0/G1 phase in anti-CD3 monoclonal antibody-stimulated PBMC
cultures in controls and in 15 of 18 HIV-infected children.
Spontaneous- or activation-induced apoptosis of PBMCs from HIV-infected
or uninfected individuals or of Fas-induced apoptosis in Jurkat and PM1
T cell lines were not inhibited by IDV. Moreover, IDV did not inhibit
activation of caspases-1, -3, -4, -5, -9, and -8 in lysates of Jurkat T
cells undergoing Fas-induced apoptosis. The findings indicate that IDV interferes with cell-cycle progression in primary cells but does not
directly affect apoptosis. It is concluded that IDV may prolong cell
survival indirectly by inhibiting their entry into cell cycle. In individuals on PI therapy, PI-mediated effects could potentially modulate immunologic responses independently of antiviral activity against HIV.
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