CD4(+) T cells from food allergy model are resistant to TCR-dependent apoptotic induction.

ABSTRACT

BACKGROUND: CD4(+) T cell polarization plays a critical role in the pathogenesis of allergy. How to modulate the skewed CD4(+) T cell polarization is less clear. The specific immunotherapy (SIT) is the only specific remedy for the treatment of allergic diseases; the therapeutic effect is to be improved. OBJECTIVES: This study aims to investigate the role of interleukin (IL)-18 in enhancing the therapeutic effect of SIT. METHODS: A peanut allergy mouse model was developed and treated with SIT or/and IL-18. CD4(+) T cell apoptosis was assessed by flow cytometry. The expression of Fas ligand (FasL) was observed by quantitative real time RT-PCR and Western blotting. Interferon-γ in the culture medium was determined by enzyme-linked immunosorbent assay. The fasL gene promoter methylation in CD4(+) T cells was assessed by methylation specific PCR. RESULTS: The results showed that lower levels of IL-18 were detected in allergic mice; administration of IL-18 significantly enhanced the therapeutic effect of SIT on suppressing the allergic inflammation in the mouse intestine. In the cell culture studies, IL-18 increased the TCR-dependent CD4(+) T cell apoptosis, the expression of FasL in CD4(+) T cells, the production of Interferon-γ and the demethylation of the FasL promoter in CD4(+) T cells. CONCLUSIONS: Administration of IL-18 enhances the effect of SIT on suppressing allergic inflammation in the mouse intestine via enhancing the TCR-dependent CD4(+) T cell apoptosis.