IL-15 promotes cytokine production of human T helper cells

IL-15 is a newly identified cytokine that has T cell and B cell growth factor activity similar to that of IL-2. In this study, a novel biologic function of IL-15 to promote cytokine production by human Th cells has been elucidated. Dermatophagoides farinae 11 (a major allergen of house dust mite)-specific human T cell clones produced IL-5 in response to recombinant human IL-15 as well as to either anti-CD3 or IL-2 stimulation. IL-5 mRNA became detectable 3 h after IL-15 stimulation and reached a maximum at 9 h. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell clones was clearly transcribed in response to IL-15, indicating that the approximately 500-bp human IL-5 promoter/enhancer segment 5' upstream of the coding region sufficiently responded to IL-15. IL-15-induced IL-5 synthesis was completely inhibited by the tyrosine kinase inhibitor, herbimycin A, suggesting the involvement of tyrosine kinases in the signal transduction leading to IL-5 synthesis as well as to proliferation of T cells induced by IL-15. Whereas IL-5 production by human peripheral T cells was abolished by the addition of anti-IL-2-neutralizing Abs into the culture, IL-15 restored the IL-5 synthesis despite effective IL-2 neutralization. IL-15 produced at the site of allergic inflammation may play a role in the recruitment and activation of eosinophils by inducing IL-5 (a Th2 cytokine) production by T cells.