IL-2-INDUCED IL-5 SYNTHESIS, BUT NOT PROLIFERATION, OF HUMAN CD4(-CELLS IS SUPPRESSED BY FK506() T)

Regulation of T cell IL-5 synthesis was investigated using human Th ce ll clones. Immunosuppressant FK506 suppressed IL-5 synthesis of T cell s activated through TCR in a dose-dependent manner. IL-5 gene transcri ption and protein synthesis were also induced in the same T cell clone s upon stimulation with IL-2 and were suppressed by FK506 in a dose re sponse similar to that induced by TCR stimulation. In contrast to TCR stimulation, neither activating protein-1, nuclear factor-AT (NF-AT), nor NF-kappa B binding activity was significantly up-regulated by IL-2 stimulation. Human IL-5 promoter/enhancer-luciferase gene construct t ransfected to T cell clones was transcribed upon either TCR or IL-2 st imulation and was clearly down-regulated by FK506, indicating that the approximately 500-bp human IL-5 gene segment located 5' upstream of t he coding region contained FK506-sensitive enhancer elements. Our pres ent findings clearly indicate that FK506-sensitive signaling molecules are involved in T cell IL-5 production induced by both TCR and IL-2 s timulation and suggest that IL-2 receptor signal leading to IL-5 gene transcription is transduced by a unique FK506-sensitive pathway other than the Ca2+-dependent signal transduction pathway, such as the calci neurin-NF-AT system.