IL-18Ralpha Mediated GATA-3 Induction by Th2 Cells: IL-12 Supports IL-18Ralpha Expression in Th2 Cells.
- Author:
In Sook JOO
1
;
Min Jung SUN
;
Dong Young KIM
;
Su Jin LEE
;
Youn Mun HA
;
Jeong Je CHO
;
Cheung Seog PARK
;
Hyun Jong AHN
Author Information
- Publication Type:Original Article
- Keywords: IL-18Ralpha; GATA-3; IL-18; IL-12; Th
- MeSH: Binding Sites; Clone Cells; Interleukin-12*; Interleukin-18; Interleukin-4; RNA, Messenger; T-Lymphocytes; Th2 Cells*; Up-Regulation
- From:Immune Network 2005;5(1):16-22
- CountryRepublic of Korea
- Language:Korean
- Abstract: BACKGROUND: IL-18 was originally cloned as a IFN-gamma inducing factor in primed T cells. In synergy with IL-12, IL-18 has been shown to induce strikingly high levels of IFN-gamma production by T cells and to enhance Th1 development. Also this cytokine exerts induction of Th2 development through IL-4 induction. METHODS: Resting CD4+ T cells were sorted by negative selection and activated by anti-CD3 plus anti-CD28 Ab. Expression of IL-12 binding sites, IL-18 binding sites, IL-18Ralpha, and GATA-3 mRNA were analysed by FACS and RT-PCR, respectively. RESULTS: Resting CD4+ T cells expressed IL-18Ralpha chain but not IL-18 binding sites, suggesting a lack of IL-18Rbeta expression. IL-18Ralpha was maintained on the Th1 and Th2 committed cells. IL-18 binding sites were induced on the Th1 but not Th2 cells. Exposure of these cells to IL-18 led to up-regulation of GATA-3 mRNA expression only in Th2 committed cells. To elucidate the relationship between IL-18Ralpha expression and GATA-3 induction by IL-18, Th1 and Th2 committed cells were further cultured in medium with or without IL-12 for 2 days. IL-12 binding sites were maintained on the Th1 and Th2 cells regardless of IL-12 treatment, but IL-18Ralpha expression was rapidly down-regulated on the IL- 12-untreated Th2 cells which did not induce GATA-3 mRNA expression followed by IL-18 stimulation. CONCLUSION: IL-12 supports expression of IL-18Ralpha and GATA-3 mRNA expression was induced by IL-18 through IL-18Ralpha without expression of IL-18 binding site in Th2 cells.
