Here we term these cells “Multiple CytokineProducing Hepatic T Cells”. In the liver, unique and organ-specific immune systems, composed of specialized cells such as Kupffer cells, NK cells, or NKT cells, are present, showing an immunological environment unlike that of any other immune competent organs or tissues. Constitutive exposure of large amounts of both enteric and systemic blood-borne antigens does not induce intense activation of the hepatic immune system, indicating the existence of strict regulation machineries in the liver. Upon the disruption of these regulatory machineries by infection with some pathogens such as the hepatitis B virus, runaway immune reactions are induced in the liver, resulting in fulminant hepatitis. The molecular mechanisms underlying such phenomena remain to be elucidated. Schistosome infection begins with direct penetration of the host skin by the cercariae. Subsequently, the schistosomes invade blood vessels and reach the hepatic portal vein, where they mature, mate, and produce eggs. Oviposition in S. mansoni starts 4–6 weeks after the initial cercarial infection. Approximately 300 eggs a day are laid by one female fluke, and many of them enter the liver via the blood. Antigens derived from both the worms and the eggs accumulate in the liver. Fibrotic granulomatous disorders in the liver are the most significant and serious etiology of S. mansoni infection, although chronic inflammatory lesions are sometimes observed in several other organs. In a S. mansoni-infected host, Th1- and Th2-related responses are evoked during different infectious periods. In the early phase, Th1-related responses are induced. As oviposition begins, the Th1 components are gradually down-regulated, and Th2 reactions become dominant in the late phase. Several previous reports indicate that the immunological balances between Th1 and Th2 responses in S. mansoni-infected hosts have implications for severity of pathology. Intriguingly, the MCPHT cells that we recently reported were found to expand during the period between Th1- and Th2-dominant phases, which we term the “transition phase”. Here, we show that IL-18 contributes to the expansion of MCPHT cells that are induced during S. mansoni infection. Levels of IL-18 in the liver and sera are elevated during the transition phase of the infection, when a significant expansion of MCPHT cells occurs. IL-18-deficient mice displayed severely impaired expansion of MCPHT cells during S. mansoni infection. Therefore, our present studies suggest that IL-18 induced during S. mansoni infection play a role for the expansion of MCPHT cells within the liver of the host. It is thought that Th1- and Th2-responses are incompatible in one immunological circumstance, and that single T cells are ordinarily incapable of producing IFN-c and IL-4, the most typical Th1- and Th2-related cytokines respectively, simultaneously.