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: B M Sharp, K McAllen, G Gekker, N A Shahabi, P K Peterson
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 167 Issue 2 Pg. 1097-102 (Jul 15 2001) ISSN: 0022-1767 [Print] United States
• PMID: 11441121 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-HIV Agents
• Immunosuppressive Agents
• Phytohemagglutinins
• Receptors, Opioid, delta

Topics

• Anti-HIV Agents (blood)
• CD4-Positive T-Lymphocytes (immunology, metabolism, virology)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cells, Cultured
• Flow Cytometry
• Fluorescent Antibody Technique, Direct (methods)
• HIV-1 (immunology)
• Humans
• Immunologic Memory
• Immunosuppressive Agents (blood)
• Interphase (immunology)
• Lymphocyte Activation
• Male
• Phytohemagglutinins (pharmacology)
• Receptors, Opioid, delta (biosynthesis, blood, physiology)
• Signal Transduction (immunology)
• Virus Replication (immunology)