T cells enhance production of IL-18 by monocytes in response to an intracellular pathogen

We studied the effect of T cells on IL-18 production by human monocytes in response to Mycobacterium tuberculosis. Addition of activated T cells marke dly enhanced IL-18 production by monocytes exposed to M. tuberculosis. This effect was mediated by a soluble factor and did not require cell-to-cell c ontact. The effect of activated T cells was mimicked by recombinant IFN-gam ma and was abrogated by neutralizing Abs to IFN-gamma. IFN-gamma also enhan ced the capacity of alveolar macrophages to produce IL-18 in response to Al . tuberculosis, suggesting that this mechanism also operates in the lung du ring mycobacterial infection. IFN-gamma increased IL-18 production by incre asing cleavage of pro-IL-18 to mature IL-18, as it enhanced caspase-1 activ ity but did not increase IL-18 mRNA expression. These findings suggest that activated T cells can contribute to the initial immune response by augment ing IL-18 production by monocytes in response to an intracellular pathogen.