IL-4-dependent up-regulation of IL-4 receptor expression in murine T and B cells

This study examined mRNA levels and cell surface expression of IL-4 receptor (IL-4R) in murine T and B cells after incubation with IL-4. Northern blot analysis of mRNA levels of T cells isolated from mesenteric lymph nodes and spleen revealed that IL-4 induced a transient augmentation of IL-4R mRNA in a dose-dependent manner. Maximal levels of mRNA were detected as early as 5 h after initiation of culture. These data were complemented by studies examining the cell surface expression of IL-4R using an anti-IL-4R mAb. Resting T and B lymphocytes express IL-4R (T greater than B) and incubation of these cells with exogenous IL-4 increased IL-4R expression to a maximum after 24 h. This effect was abolished after addition of anti-IL-4 antibody. Continuous incubation of T cells in the presence of high concentrations of IL-4 resulted in a down-regulation of IL-4R expression. Addition of the protein synthesis inhibitor cycloheximide blocked the induced increases in IL-4R expression, indicating the requirement for de novo protein synthesis. Both the levels of mRNA and cell surface expression of IL-4R were not affected by addition of exogenous IL-2, and IL-4 regulation of IL-4R expression was not influenced by the immunosuppressive drug cyclosporin A. These data demonstrate that in T and B cells, IL-4 induces a transient up-regulation of IL-4 mRNA levels that is subsequently reflected in increased numbers of IL-4R displayed on the cell surface. This regulation of IL-4R expression by IL-4 provides an important mechanism for amplification of IL-4-dependent activation pathways.