IL-2-Induced IL-9 Production by Allergen-Specific Human Helper T Cell Clones

Abstract

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. Ca²⁺ signal, CD28 signal, and IL-2 receptor signal seem to play important roles on 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.

Autocrine/paracrine cytokine stimulation of leukemic cell proliferation in smoldering and chronic adult T-cell leukemia

“…Consistent with our observation, Fung et al and Kajiyama et al showed that IL-2 induced IL-9 production in HTLV-1-infected cell lines and allergen-specific human helper T-cell clones. 35,36 Further analysis of the IL-9 promoter would be helpful to identify transcriptional elements and epigenetic events that are responsible for IL-2-induced IL-9 expression.…”

Measurement of CD4+ and CD8+ T-Lymphocyte Cytokine Secretion and Gene Expression Changes in p-Phenylenediamine Allergic Patients and Tolerant Individuals

“…Gene patterns associated with the development of a Th2 cellular immune response were evident in allergic patients' samples, but absent in those from tolerant individuals (Figure 4). Networks deriving from allergic patients' samples also contained the cytokine IL-9, a signaling molecule secreted from memory T cells (Kajiyama et al, 2007) that promotes IgE production by B cells and has been implicated in allergic diseases such as asthma and food allergy (Ying et al, 2002;Forbes et al, 2008). Recently, IL-9producing T cells were found to be a distinct T-cell population, provisionally termed Th9 cells, deriving from Th2 cells following programming in the presence of TGF-b (Veldhoen et al, 2008).…”

Increased expression of nuclear factor of activated T cells 1 drives IL-9–mediated allergic asthma

“…IRF4 is known to be essential for IL-9 production, and now we found that NFATc1 also has an effect on IL-9 production either through a direct effect on the promoter of IL-9 (alone or along with IRF4) or through its influence on IL-2 E14 or IL-4, which are required for IL-9 production. In fact, TGF-β and IL-4 are required to induce T H 9 differentiation.…”