Imiquimod, a Toll-like receptor-7 agonist, induces perforin in cytotoxic T lymphocytes in vitro

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 perform in CTLs in vitro. In peripheral lymphocytes of healthy and diseased Subjects, IMQ induced a significant increase of perforin(+) CTLs within 12 h in all experiments performed. This effect was most pronounced in CTLs of patients suffering from atopic dermatitis, a model disorder for subnormal perform expression: as compared to perforin(+) CTLs detected at time point zero (100%), up to 270% of perforin(+) CTLs were induced by 2.5 muM/ml IMQ. Perforin release front 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. (C) 2004 Elsevier Ltd. All rights reserved.