Inhibitory action of deoxyspergualin on effector/memory T cell generation during Hymenolepis nana infection in mice.
The effects of deoxyspergualin (DSG), a newly developed immunosuppressive agent, on protective immunity to Hymenolepis nana reinfection were examined in BALB/c mice. Administration of DSG at daily doses of 10.0 mg/kg to 30.0 mg/kg (but not 5.0 mg/kg) caused suppression of protective immunity when the agent was injected intraperitoneally during the induction phase of the immunity. In contrast, daily administration of 30.0 mg/kg DSG, during effector phase, could not suppress protective immunity. DSG inhibited endogenous interferon-gamma production in mesenteric lymph nodes induced by H. nana challenge infection, when the agent was injected intraperitoneally at a daily dose of 10.0 mg/kg during the induction phase of immunity. Delayed type hypersensitivity (DTH) local transfer analysis revealed that administration of DSG at 10.0 mg/kg/day into donor mice during induction phase of immunity inhibited generation of effector/memory cells that mediate DTH to H. nana egg antigen. However, DSG could not inhibit DTH effector cell activation when cells prepared from H. nana-infected, saline-injected mice were transferred into recipient treated with 10.0 mg/kg DSG. Administration of DSG at a dose of 10.0 mg/kg daily for 5 days produced large DNA fragments in mesenteric lymph node (MLN) cells. These results strongly suggest that DSG suppresses generation of effector/memory cells by apoptotic cell death but cannot suppress lymphocyte activation in vivo.
Asano
K
K
Department of Medical Biology, School of Medicine, Showa University, Tokyo, Japan.
Muramatsu
K
K
Ikeda
K
K
Okamoto
K
K
D000818:Animals; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D006146:Guanidines / Q000627:therapeutic use*; D018922:HL-60 Cells; D006801:Humans; D006925:Hymenolepiasis / Q000188:drug therapy / Q000276:immunology*; D006926:Hymenolepis / Q000276:immunology*; D006968:Hypersensitivity, Delayed; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*
D006146:Guanidines; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; C037258:gusperimus