Lee M H, Kataoka T, Honjo N, Magae J, Nagai K
Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Japan.
Immunology. 2000 Feb;99(2):243-8. doi: 10.1046/j.1365-2567.2000.00961.x.
Prodigiosin (PrG) 25-C and concanamycin B (CMB) are immunosuppressants that specifically inhibit the induction of cytotoxic T cells (CTL) without affecting the function of B cells and helper T cells in vivo. Both compounds inhibit acidification of intracellular organelles and induce destruction of cytotoxic granules and degradation of perforin in vitro. Here we show that a single intraperitoneal (i.p.) injection of PrG 25-C, and of CMB, into mice eliminates cytotoxic activity 7 days after alloantigen stimulation (when mature CTL activity has been detected in control mice), with minimal effect on the alloantigen-specific antibody titre in serum. FK506 did not suppress the cytotoxic activity with this administration schedule. Suppression was accompanied by a decrease in the CD8+ population and in perforin expression of spleen cells induced by alloantigen stimulation. The suppression of CTL activity and decrease in CD8+ cell number was detected as early as 7 hr after the injection of compounds. These results suggest that inhibitors of acidification of intracellular organelles suppress CTL activity in vivo by reducing the number of mature CD8+ CTL.
灵菌红素（PrG）25 - C和康卡霉素B（CMB）是免疫抑制剂，它们在体内能特异性抑制细胞毒性T细胞（CTL）的诱导，而不影响B细胞和辅助性T细胞的功能。这两种化合物在体外均能抑制细胞内细胞器的酸化，并诱导细胞毒性颗粒的破坏和穿孔素的降解。在此我们表明，给小鼠腹腔内（i.p.）单次注射PrG 25 - C和CMB，在同种异体抗原刺激7天后（此时在对照小鼠中已检测到成熟的CTL活性）可消除细胞毒性活性，而对血清中同种异体抗原特异性抗体滴度影响最小。按照此给药方案，FK506不会抑制细胞毒性活性。抑制作用伴随着同种异体抗原刺激诱导的脾脏细胞中CD8⁺群体和穿孔素表达的减少。在注射化合物后7小时就检测到了CTL活性的抑制和CD8⁺细胞数量的减少。这些结果表明，细胞内细胞器酸化抑制剂通过减少成熟CD8⁺CTL的数量来抑制体内CTL活性。
