title: Low versus high density of immobilized anti-CD3 influences IL-4 regulation of T-cell immune responses.
abstract: Varying the concentration of anti-CD3 immobilized on Sepharose beads allowed us to study both the inhibitory and the stimulatory effects of IL-4 on purified T cells and contrast IL-4 versus IL-2-driven T-cell proliferative responses. In the presence of low density immobilized anti-CD3, IL-4 was unable to stimulate purified T cells and was inhibitory to IL-2-driven T-cell responses. The inhibitory effects of IL-4 were enhanced by preincubation of T cells with IL-4 prior to stimulation. In contrast, the inhibitory effects of IL-4 could be avoided by delaying the addition of IL-4 until Days 3-5 of culture or they could be reversed by the addition of IL-1. In the presence of high-density anti-CD3, IL-4 elicited an IL-2-independent proliferative response by purified T cells or sorted CD8+ cells. Comparison of IL-4-driven versus IL-2-driven T-cell responses demonstrated that IL-2 was able to upregulate mRNA for IL-4 receptors and interferon-gamma, while IL-4 had minimal effects on upregulating mRNA for either the p55 or the p75 IL-2 receptor subunits or interferon-gamma. The timing of the presence of IL-4, the state of T-cell activation, and the nature and strength of the stimulatory signal influenced the regulatory effect of IL-4 on the immune response.
authors.affiliation: Division of Cytokine Biology, FDA, Bethesda, Maryland 20892.
authors.forename: L A
authors.initials: LA
authors.lastname: Jones-Tiffany
authors.forename: P T
authors.initials: PT
authors.lastname: Mehrotra
authors.forename: D W
authors.initials: DW
authors.lastname: Horohov
authors.forename: J
authors.initials: J
authors.lastname: Siegel
authors.forename: R W
authors.initials: RW
authors.lastname: Kozak
mesh_terms: D017252:CD3 Complex / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
chemical_list: D017252:CD3 Complex; D007375:Interleukin-1; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D007371:Interferon-gamma