Immunofluorescence Detection of delta Opioid Receptors (DOR) on Human Peripheral Blood CD4 super(+) T Cells and DOR-Dependent Suppression of HIV-1 Expression

The delta opioid receptors (DORs) modulate T cell proliferation, IL-2 production, chemotaxis, and intracellular signaling. Moreover, in DOR-transfected Jurkat cells, delta 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 alpha ,5 beta ]}-(9Cl) (SNC-80), can suppress p24 Ag expression by HIV-1-infected CD4 super(+) T cells obtained from normal donors. By immunofluorescence flow cytometry, PHA stimulated the expression of DOR from 1.94 plus or minus 0.70 (mean plus or minus SEM) to 20.70 plus or minus 1.88% of the PBMC population by 48 h (p < 0.0001). DOR expression was approximately 40% of both the PHA-stimulated CD4 super(+) and CD8 super(+) 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 super(+) 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 super(-10) M maximally suppressed ( approximately 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 super(+) 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.