Low versus high density of immobilized anti-CD3 influences IL-4 regulation of T-cell immune responses

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-γ, while IL-4 had minimal effects on upregulating mRNA for either the p55 or the p75 IL-2 receptor subunits or interferon-γ. 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.