Regulation of HIV production by blood mononuclear cells from HIV-infected donors: I. Lack of correlation between HIV-1 production and T cell activation.
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.
Moran
P A
PA
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Diegel
M L
ML
Sias
J C
JC
Ledbetter
J A
JA
Zarling
J M
JM
D001782:Blood Donors; D017252:CD3 Complex; D016207:Cytokines / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology / Q000382:microbiology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D017493:Leukocyte Common Antigens; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014779:Virus Replication
D017252:CD3 Complex; D016207:Cytokines; D017493:Leukocyte Common Antigens