In vivo rapid reduction of alloantigen-activated CD8+ mature cytotoxic T cells by inhibitors of acidification of intracellular organelles, prodigiosin 25-C and concanamycin B.
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.
Lee
M H
MH
Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Japan.
Kataoka
T
T
Honjo
N
N
Magae
J
J
Nagai
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology; D018655:Lymphocyte Count / Q000187:drug effects; D018942:Macrolides; D051379:Mice; D008810:Mice, Inbred C57BL; D015388:Organelles / Q000187:drug effects / Q000378:metabolism; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D007519:Isoantigens; D018942:Macrolides; C077331:prodigiosin 25C; C036979:concanamycin B; D011353:Prodigiosin