Immunomodulative effect of cholera toxin in mice
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WS3-6 "6 INDUCTION OF ANTITUMOR EFFECTOR CELLS BY OK-432 Y.Moriya*,K.Nunomura*,M.Nanjo**,M.Kataoka*,M.Saito*,**,Y.Sugawara* T.Yoshida**,N.Ishida*** *Applied Res. Labs. Chugai Pharm. Co. Ltd.,Tokyo,Japan **Tokyo Inst. for Immunopharm. Tokyo,Japan ***Tohoku Univ. Sendai,Japan The nature of antitumor effector cells induced by OK-432, a streptococcal preparation with potent BRM activity, was analysed. BALB/c-+/+ mice implanted(ip) with syngeneic fibrosarcoma BAMC-I were cured by 5 every other day injections(ip) of 0K-432 starting day2 after tumor implantation. In the case of BALB/c-nu/nu mice, however, the number of tumor cells decreased transiently until dayS, then rapidly increased finally causing death of the host. When peritoneal exudate cells(PEC) of +/÷ mice treated as above were transferred into peritoneal cavity of nu/nu mice treated similarly as +/+ mice on or after day7 of tumor implantation, more than 85% of the recipients were survived. The effector cells in the PEC were nylon wool column non- adherent, and had surface markers as ThyI÷,L3T4+,Lyt2-,AsGMI-,LAA + cells. Therfore it is concluded that induction of L3T4 ÷ cells at tumor site may be essential for tumor eradication by OK-432 in this system. WS3-7 *7 ROLE OF NK CELLS IN THE ANTITUMOR ACTIVITY OF A NUCLEIC ACID FRACTION FROM BCG E. Kuramoto, S. Shimada, and T. Tokunaga* Inst. Biological Science, Mitsui Pharmaceuticals Inc., Mobara,Chiba, Japan; *Dept. Cellular Immunology, National Inst. Health, Tokyo, Japan A fraction extracted from BCG and designated MY-l, which was composed of 70% DNA and 28% RNA, was previously reported to have strong antitumor activities against various syngeneic mouse and guinea pig tumors and to have no direct cytotoxicity to the tumor cells. To clarify the mechanism of its antitumor activity, role of NK cells was investigated. When EL4 tumor cells were inoc- ulated together with MY-I into C57BL/6 mice, the tumor growth was markedly suppressed. This tumor suppression was abrogated by pretreatment of the mice with anti-asialo GMI antibody. MY-I showed no such activity in NK-deficient beige mice, but the activity was restored by transfer of untreated C57BL/6 spleen cells, but not by those pretreated with anti-asialo GMI and comple- ment. Intralesional injection of MY-I into Meth A tumor of BALB/c mice re- gressed the tumor and augmented NK activity of cells in the tumor-draining lymph nodes, but not in the remote lymph nodes. MY-I also induced an infil- tration of asialo GMl-positive, NK-like cells at the injection site. These results indicate that NK cells activated by MY-I play an important role in the antitumor activity of MY-I WS3-8 *s IMMUNOMODULATIVE EFFECT OF CHOLERA TOXIN IN MICE A.Hussain, K.Himeno, N.Tokuda, T.Asano, and K.Nomoto. Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan Immunomodulative effect of cholera toxin (CT) was examined in mice using various immunological parameters. C3H/He mice were injected 2ug of CT at various intervals before assay (Day-21 to Day 0). Thymocytes were markedly decreased in number and phenotypes in such cells were clearly shifted from "cortical type" to "medullary type" in Day-2 and Day-4 treated groups. Spleen T cells were relatively increased, especially in Lyt-1 and Lyt-2 fractions, while surface IgM positive B cells were rather decreased. Natural killer activity or in vivo and in vitro cytotoxic T cell activity were markedly suppressed in early stages after CT treatment but completely recovered withen 21 days. Mixed lymphocyte reaction (MLR) was profoundly suppressed in all groups. Furthermore, EL-4 tumor of C57BL/6 origin grew progressively and killed the host mice when such tumor cells were inoculated on Day 0. On the contrary, marked augmentation of PFC and delayed type hypersensitivity (DTH) to SRBC was seen in all treated mice. Taken together, CT appears to have an immunomodulative effect suppressing class-I restricted immune responses like cytotoxic T cell activity and augmenting class-II restricted immune responses like helper T activity and DTH. 84
Transcript of Immunomodulative effect of cholera toxin in mice
WS3-6 "6 INDUCTION OF ANTITUMOR EFFECTOR CELLS BY OK-432 Y.Moriya*,K.Nunomura*,M.Nanjo**,M.Kataoka*,M.Saito*,**,Y.Sugawara* T.Yoshida**,N.Ishida*** *Applied Res. Labs. Chugai Pharm. Co. Ltd.,Tokyo,Japan **Tokyo Inst. for Immunopharm. Tokyo,Japan ***Tohoku Univ. Sendai,Japan The nature of antitumor effector cells induced by OK-432, a streptococcal preparation with potent BRM activity, was analysed. BALB/c-+/+ mice implanted(ip) with syngeneic fibrosarcoma BAMC-I were cured by 5 every other day injections(ip) of 0K-432 starting day2 after tumor implantation. In the case of BALB/c-nu/nu mice, however, the number of tumor cells decreased transiently until dayS, then rapidly increased finally causing death of the host. When peritoneal exudate cells(PEC) of +/÷ mice treated as above were transferred into peritoneal cavity of nu/nu mice treated similarly as +/+ mice on or after day7 of tumor implantation, more than 85% of the recipients were survived. The effector cells in the PEC were nylon wool column non- adherent, and had surface markers as ThyI÷,L3T4+,Lyt2-,AsGMI-,LAA + cells. Therfore it is concluded that induction of L3T4 ÷ cells at tumor site may be essential for tumor eradication by OK-432 in this system.
WS3-7 *7 ROLE OF NK CELLS IN THE ANTITUMOR ACTIVITY OF A NUCLEIC ACID FRACTION FROM BCG E. Kuramoto, S. Shimada, and T. Tokunaga* Inst. Biological Science, Mitsui Pharmaceuticals Inc., Mobara,Chiba, Japan; *Dept. Cellular Immunology, National Inst. Health, Tokyo, Japan A fraction extracted from BCG and designated MY-l, which was composed of 70% DNA and 28% RNA, was previously reported to have strong antitumor activities against various syngeneic mouse and guinea pig tumors and to have no direct cytotoxicity to the tumor cells. To clarify the mechanism of its antitumor activity, role of NK cells was investigated. When EL4 tumor cells were inoc- ulated together with MY-I into C57BL/6 mice, the tumor growth was markedly suppressed. This tumor suppression was abrogated by pretreatment of the mice with anti-asialo GMI antibody. MY-I showed no such activity in NK-deficient beige mice, but the activity was restored by transfer of untreated C57BL/6
spleen cells, but not by those pretreated with anti-asialo GMI and comple- ment. Intralesional injection of MY-I into Meth A tumor of BALB/c mice re- gressed the tumor and augmented NK activity of cells in the tumor-draining lymph nodes, but not in the remote lymph nodes. MY-I also induced an infil- tration of asialo GMl-positive, NK-like cells at the injection site. These results indicate that NK cells activated by MY-I play an important role in the antitumor activity of MY-I
WS3-8 *s IMMUNOMODULATIVE EFFECT OF CHOLERA TOXIN IN MICE A.Hussain, K.Himeno, N.Tokuda, T.Asano, and K.Nomoto. Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan Immunomodulative effect of cholera toxin (CT) was examined in mice using various immunological parameters. C3H/He mice were injected 2ug of CT at various intervals before assay (Day-21 to Day 0). Thymocytes were markedly decreased in number and phenotypes in such cells were clearly shifted from "cortical type" to "medullary type" in Day-2 and Day-4 treated groups. Spleen T cells were relatively increased, especially in Lyt-1 and Lyt-2 fractions, while surface IgM positive B cells were rather decreased. Natural killer activity or in vivo and in vitro cytotoxic T cell activity were markedly suppressed in early stages after CT treatment but completely recovered withen 21 days. Mixed lymphocyte reaction (MLR) was profoundly suppressed in all groups. Furthermore, EL-4 tumor of C57BL/6 origin grew progressively and killed the host mice when such tumor cells were inoculated on Day 0. On the contrary, marked augmentation of PFC and delayed type hypersensitivity (DTH) to SRBC was seen in all treated mice. Taken together, CT appears to have an immunomodulative effect suppressing class-I restricted immune responses like cytotoxic T cell activity and augmenting class-II restricted immune responses like helper T activity and DTH.
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