INTERLEUKIN-4 (IL) 4 UP-REGULATES GENE AND SURFACE IL-1 RECEPTOR TYPE-I IN MURINE T-HELPER TYPE-2 CELLS

The T cell-derived cytokine interleukin (IL) 4 is known to increase the proliferative response of T cells stimulated with IL 1. IL 4 is also an autocrine growth factor for type II T helper cells (T(h)2) cells. In the present studies, we examined the effect of murine recombinant IL 4 on the expression of the IL 1 receptor type I (IL 1RtI) in murine T(h)2 cell lines at the mRNA and surface level. Using a specific anti-murine IL 1RtI monoclonal antibody and flow microfluorometry, we found that IL 4 increased the surface expression of IL 1RtI in a dose-dependent manner. In D10S cells, a subline of the T(h)2 cell line D10.G4.1, 50-500 pg/ml IL 4 up-regulated the receptor 1.8- to 3.2-fold (p < 0.05). This up-regulation was also seen at the mRNA level. The effect was not due to increased stability of the mRNA, since IL 4 did not modify the half-life of IL 1RtI mRNA. IL 4 also up-regulated IL 1RtI on CDC25 cells, another T(h)2 cell line. However, we did not observe an effect of IL 4 on gene expression of IL 1RtI in BALB/c 3T3 fibroblasts. IL 2 and IL 4 showed an additive effect in up-regulating IL 1RtI and D10S cells. These studies indicate that IL 4 up-regulates IL 1RtI in murine T(h)2 cells by increasing gene expression for IL 1RtI without affecting mRNA stability. Thus, IL 4 production by T(h)2 cells may amplify the immune response via up-regulation of IL 1RtI.