Regulation of HIV production by blood mononuclear cells from HIV-infected donors: I. Lack of correlation between HIV-1 production and T cell activation.

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Regulation of HIV production by blood mononuclear cells from HIV-infected donors: I. Lack of correlation between HIV-1 production and T cell activation.

AIDS Res Hum Retroviruses. 1993 May;9(5):455-64. Unique Identifier : AIDSLINE MED/93305385
Moran PA; Diegel ML; Sias JC; Ledbetter JA; Zarling JM; Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle,; WA 98121.

Abstract: The relationship between production of HIV-1 by peripheral blood mononuclear cells (PBMCs) from HIV-1-infected donors and the level of T cell activation by various stimuli was examined. Stimulation of PBMCs with soluble anti-CD3 antibody or staphylococcal enterotoxin/superantigen (SAg) was found to be 100-1000 times more effective at inducing production of HIV-1 than was stimulation with immobilized anti-CD3 or various other T cell activating agents. However, proliferation of CD4+ T cells and lymphokine production following stimulation with soluble anti-CD3 were less than with immobilized anti-CD3. To determine whether immobilized anti-CD3 stimulated cells may produce a factor(s) that suppresses HIV production, dual-chamber coculture experiments were performed in which soluble and immobilized anti-CD3-stimulated CD8-depleted PBMCs were separated by porous membranes. Stimulation of cells by immobilized anti-CD3 suppressed HIV-1 production by soluble anti-CD3-stimulated cells in the inner chamber, suggesting that diffusible factor(s) are involved in suppressing HIV-1 production. Experiments in which exogenous cytokines were added to cells stimulated with soluble anti-CD3 did not reveal the suppressive factor(s) produced; however, IL-7 was found to markedly increase HIV-1 production. Both T cells and monocytes were found to be required for soluble anti-CD3 to induce high levels of HIV-1 production, suggesting a role for adhesion molecules. Our results thus show that (1) soluble anti-CD3 is a powerful stimulus for HIV production, (2) there is not an absolute correlation between the level of HIV-1 production and T cell activation following stimulation of PBMCs with T cell activating agents, (3) immobilized anti-CD3 stimulation produces a factor that decreases HIV replication, and (4) T cell monocyte interactions are important for production of HIV-1 following stimulation with soluble anti-CD3.

Keywords: Antigens, CD3 Antigens, CD45 Blood Donors Cytokines/PHARMACOLOGY Human HIV Infections/IMMUNOLOGY/*MICROBIOLOGY HIV-1/IMMUNOLOGY/*PHYSIOLOGY In Vitro Leukocytes, Mononuclear/IMMUNOLOGY/MICROBIOLOGY Lymphocyte Transformation Monocytes/IMMUNOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocyte Subsets/IMMUNOLOGY Virus Replication JOURNAL ARTICLE
931030
M93A0723

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