Due to their innovative functions, the use of nanoparticles in various industries has been expanding. However, a key concern is whether nanoparticles induce unexpected biological effects. Although many studies have focused on innate immunity, information on whether nanoparticles induce biological responses through effects on acquired immunity is sparse. Here, to assess the effects of amorphous silica nanoparticles on acquired immunity, we analyzed changes in acute toxicities after pretreatment with amorphous silica nanoparticles (50 nm in diameter; nSP50). Pretreatment with nSP50 biochemically and pathologically exacerbated nSP50-induced hepatic damage in immunocompetent mice. However, pretreatment with nSP50 did not exacerbate hepatic damage in immunodeficient mice. Consistent with this, the depletion of CD8+ cells with an anti-CD8 antibody in animals pretreated with nSP50 resulted in lower plasma levels of hepatic injury markers such as ALT and AST after an intravenous administration than treatment with an isotype-matched control antibody. Finally, stimulation of splenocytes promoted the release of IFN-γ in nSP50-pretreated mice regardless of the stimulator used. Moreover, the blockade of IFN-γ decreased plasma levels of ALT and AST levels in nSP50-pretreated mice. Collectively, these data show that nSP50-induced acquired immunity leads to exacerbation of hepatic damage through the activation of cytotoxic T lymphocytes.
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