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  • Title: Imiquimod, a Toll-like receptor-7 agonist, induces perforin in cytotoxic T lymphocytes in vitro.
    Author: Ambach A, Bonnekoh B, Nguyen M, Schön MP, Gollnick H.
    Journal: Mol Immunol; 2004 Apr; 40(18):1307-14. PubMed ID: 15072849.
    Abstract:
    Imiquimod (IMQ), an activator of Toll-like receptor-7 (TLR-7), induces by several routes a profound anti-viral and anti-tumor effect in vivo. Physiologically, the immune system is using perforin-containing granules of cytotoxic T lymphocytes (CTL) towards the same biological purpose. This functional synergism prompted our current experiments addressing the question whether IMQ may influence perforin-release and/or induce perforin in CTLs in vitro. In peripheral lymphocytes of healthy and diseased subjects, IMQ induced a significant increase of perforin(+) CTLs within 12h in all experiments performed. This effect was most pronounced in CTLs of patients suffering from atopic dermatitis, a model disorder for subnormal perforin expression: as compared to perforin(+) CTLs detected at time point zero (100%), up to 270% of perforin(+) CTLs were induced by 2.5 microg/ml [corrected] IMQ. Perforin release from peripheral blood CTLs after PMA/ionomycin-stimulation was not influenced significantly by IMQ. Thus, the biological activity of IMQ appears to exceed its previously known functions, inasmuch as it boosts up significantly the perforin-granule system.
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