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Opioid Receptors (DOR) on Human Peripheral Blood CD4+ T Cells and DOR-Dependent Suppression of HIV-1 Expression1
*
Department of Pharmacology, Health Science Center, University of Tennessee, Memphis, TN 38120; and
Department of Medicine, Hennepin County Medical Center and University of Minnesota, Minneapolis, MN 55415
The 
opioid receptors (DORs) modulate T cell proliferation, IL-2
production, chemotaxis, and intracellular signaling. Moreover, in
DOR-transfected Jurkat cells, opioids have been shown to suppress
HIV-1 p24 Ag expression. These observations led us to characterize the
expression of DORs by human peripheral blood T cells and to determine
whether a specific DOR agonist,
benzamide,4-{[2,5-dimethyl-4-(2-propenyl)-1-piperazinyl](3-methoxyphenyl)methyl]-N,-,{2S[1(S*),2
,5
]}-(9Cl)
(SNC-80), can suppress p24 Ag expression by HIV-1-infected
CD4+ T cells obtained from normal donors. By
immunofluorescence flow cytometry, PHA stimulated the expression of DOR
from 1.94 ± 0.70 (mean ± SEM) to 20.70 ± 1.88% of
the PBMC population by 48 h (p < 0.0001). DOR
expression was 
40% of both the PHA-stimulated CD4+ and
CD8+ T cell subsets, and virtually all DORs were found on
these subsets. To determine whether activated DORs suppress HIV-1
expression, PBMC were prestimulated with PHA, and then CD4+
T cells were purified, pretreated with SNC-80, and infected with HIV-1.
In a concentration-dependent manner, SNC-80 inhibited production of p24
Ag. SNC-80 10-10 M maximally suppressed (50%) both
lymphocytotropic (HIV-1 MN) and monocytotropic (SF162) strains; higher
concentrations were less effective. Naltrindole, a selective DOR
antagonist, abolished the inhibitory effects of SNC-80. Kinetic studies
indicated that 24-h pre- or postincubation with SNC-80, relative to
infection with HIV-1, eliminated its suppressive effects. Thus,
stimulating the DORs expressed by activated CD4+ T cells
significantly suppressed the expression of HIV-1. These findings
suggest that opioid immunomodulation directed at host T cells may be
adjunctive to standard antiviral approaches to HIV-1
infection.
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