Interleukin-12 upregulates the IL-18R beta chain in BALB/c thymocytes

Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an importan t role in innate immunity and specific Th1 immune responses. During infecti on, IL-18 is produced by activated macrophages and primarily induces interf eron-gamma (IFN-gamma) production in synergy with IL-12 in primed T cells a nd natural killer (NK) cells. IL-18 exerts its function by binding to a spe cific receptor complex (IL-18R) consisting of two subunits, the IL-18R alph a chain and the IL-18R beta chain. Two individual mechanisms for synergism between IL-12 and IL-18 have been reported. First, IL-12-induced expression of the IL-18 receptor complex was described. Second, IL-18 and IL-12 toget her induced expression of target genes on a transcriptional level. In this study, we show that freshly isolated thymocytes from BALB/c mice constituti vely expressed mRNA for the IL-18R alpha chain but not for the IL-18R beta chain. These thymocytes were unresponsive to IL-18. Treatment with a combin ation of concanavalinA (ConA) plus IL-12 did not affect expression of the I L-18R alpha chain but strongly induced expression for IL-18R beta mRNA, ren dering these thymocytes highly responsive to IL-18 treatment. Thus, the syn ergistic effects of IL-12 and IL-18 on BALB/c mouse thymocytes resulted fro m the induction and regulation of the IL-18R beta chain and not the IL-18R alpha chain.