title: Immunofluorescence detection of delta opioid receptors (DOR) on human peripheral blood CD4+ T cells and DOR-dependent suppression of HIV-1 expression.
abstract: 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*),2alpha,5beta])-(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 approximately 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 (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+ 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.
authors: Department of Pharmacology, Health Science Center, University of Tennessee, 874 Union Avenue, Memphis, TN 38163, USA. bsharp@utmem.edu
authors: B M
authors: BM
authors: Sharp
authors: K
authors: K
authors: McAllen
authors: G
authors: G
authors: Gekker
authors: N A
authors: NA
authors: Shahabi
authors: P K
authors: PK
authors: Peterson
mesh_terms: D019380:Anti-HIV Agents / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct / Q000379:methods; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000097:blood*; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000096:biosynthesis / Q000097:blood* / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D017465:Receptors, Opioid, delta