Background: IL-9 is an important cytokine in allergic diseases such as asthma, atopic dermatitis, etc. T helper (Th) cells seem to be the main source of IL-9. Cellular and molecular mechanisms of IL-9 production by human Th cells have been poorly understood.
Methods: Dermatophagoides farinae(Der f)-specific Th clones were established from peripheral blood lymphocytes of atopic asthmatics, and cytokine synthesis in response to various stimuli was determined by specific ELISAs.
Results: IL-9 was produced by 14 of 27 human Th clones upon T cell receptor (TCR) stimulation, immobilized anti-CD3 antibody (Ab). IL-9 production was significantly enhanced by the addition of anti-CD28 Ab into the culture, indicating the role of costimulatory signal on IL-9 synthesis. Pharmacologically, IL-9 production was induced by ionomycin (IOM) alone, and enhanced by phorbol 12-myristate 13-acetate (PMA). rIL-2 induced IL-9 production by 8 out of 19 Th clones. IL-9 production by Th clones stimulated with immobilized anti-CD3 Ab was significantly suppressed by the addition of anti-IL-2 neutralizing Ab into the culture.
Conclusion: Approximately half of the Der f-specific Th clones derived from atopic asthmatics produced IL-9 upon TCR stimulation. Ca(2+) signal, CD28 signal, and IL-2 receptor signal seem to play important roles in IL-9 production by human Th cells. Moreover, synthesis of IL-9, a Th2 cytokine, is dependent on IL-2, a Th1 cytokine, which is produced by Th cells themselves.