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Lentinan, a distinct T cell oriented immunopotentiator; its immunopharmacological action
267
LENTINAN, A DISTINCT T CELL ORIENTED I~UNOPOTENTIATOR; ITS IMMUNOPHARMACOLOGICAL ACTION
60
J.Hamuro and G.Chihara, Basic Immunol. Res. Div., Yokohama and National Cancer Center Res. Inst., Tokyo, Japan Lentinan augments the reactivity of precursor effector cells responding to two major lymphokines,"Interleukin 2"(IL2) and "macrophage activating factor"(MAF) produced by activated clones of T cells, resulting in the augmented generation of "cytotoxic T lymphocytes"(CTL),"natural k i l l e r cells"(NK) and activated macrophages". Thus lentinan exerts ~ugmentation of tumor specific and non-specific, but selective effector cells induction. Lentinan triogers increased production of "Interleukin l " ( I L l ) by direct impact on macrophages (M~) or indirectly by augmented colony stimulating factor (CSF) production from lentinan stimulated T cells. Thus increased production of ILl results in augmented maturation of premature lymphoid cells into mature cells capable to differentiate into effector cells, resulting in the formation of amplification loop to induce IL2 responder and producer mature T cells. In nu/nu this amplification loop may not function. In actual, serum factors functioning to augment the reactivity of precursor cells to lymphokines were detected only in nu/~ intact in immunocompetent T cell compartment. The proposed mode of action well explains characteristics of antitumor action of lentinan. ANTIVIRAL AND ANTITUMOR ACTIVITIES INDUCED BY LENTINAN AND THEIR POSSIBLE MEO4ANISMS
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Kenneth S. S. Chang Viral Oncogenesis Section, Lab. of Cell Biology, NCI, NIH, Bethesda, MD. 2020S, USA Lentinan, a glucan derived from fruit bodies or mycelia of basidiomycet~s, Lentinus edodes (Berk) Sing., was tested for its antiviral and antitumor activities in mice. Daily i.p. injections of lentinan in mice postinfection afforded a significant degree of protection against encephalitis caused by the intranasally infected vesicular stomatitis virus. Pretreatment in addition to postinfection treatment was more effective than the latter alone. Lentinan treatment also markedly improved the survival of CF-I mice transplanted with allogeneic trophoblastic tumor cells which lacked H-2 antigen expression and are insusceptible to alloiwanune T cells. The natural killer (NK) cell activity, to which the trophoblast cells are fully susceptible, was markedly enhanced by lentinan. Although daily post-transplantation treatment with lentinan showed no protection of BALB/c mice against transplanted sFngeneic Abelson tumor, I0 daily injections of lentinan after an immunizing dose of Abelson virus have potentiated its immunizing capacity, resulting in a significant reduction in the size of tumor developing after Abelson tumor challenge. In addition to its potentiating effect on macrophages, and T and NK cells, lentinan may activate target spleen cells for Abelson virus replication and transformation, so that enhanced antigenic stimulation of the host is effected.
GLUCANS II AUGMENTATION OF INTERLEUKIN l PRODUCTION BY ANTITUMOR POLYSACCHARIDE, LENTINAN AND ITS ROLES IN THE GENERATION OF EFFECTOR T CELLS AGAINST TUMORS
I R.Yoshimoto,ly.Akiyan~,2T.Hayami,ly.Iguchi,lM.Izawa and 1j.Hamuro2
Central Research Laboratories, Ajinomoto Co., Inc., Yokohama and Research Laboratories Morishita Pharmaceutical Co. Ltd., Yasu-cho, Shiga, Japan.
The production by lentinan(LNT) of interleukin l ( I L l ) was investigated in detail. Both of peritoneal adherent cells(PC) harvested from LNT treated mice induced augmented ILl production, showingapeak augmentation on day3. Similarly, significant augmentation of ILl production by LNT was observed when PC was co-cultured in vitro withRcritical concentration of LNT in 48hrs. PC deleted of T cells(anti-Thyl+C') and macrophage cell line P388Dl induced augmented production of ILl when co-cultured with LNT. Thus LNT acts on macrophages (MB) directly to augment the production of ILl. Colony stimulating factor(s)(CSF) produced from LNT stimulated T cells also augmented the production of ILl from M~. Therefore LNT triggers increased production of ILl by direct impact on M~ or indirectly via augmented CSF production from LNT stimulated T cells synergistically. To evaluate the role of this augmented production of ILl by LNT, generation of a l l o k i l l e r cells from thymocytes was investigated. As anticipated, thymocytes harvested from responder mice treated with LNT induced augmented generation of all o k i l l e r cells in the presence of IL2 during 5day MLC. In conclusion, LNT promotes differentiation of premature T cells into immunocompetent ~ture T cells in periphery via ILl production.
61
LENTINAN, A DISTINCT T CELL ORIENTED I~UNOPOTENTIATOR; ITS IMMUNOPHARMACOLOGICAL ACTION
60
J.Hamuro and G.Chihara, Basic Immunol. Res. Div., Yokohama and National Cancer Center Res. Inst., Tokyo, Japan Lentinan augments the reactivity of precursor effector cells responding to two major lymphokines,"Interleukin 2"(IL2) and "macrophage activating factor"(MAF) produced by activated clones of T cells, resulting in the augmented generation of "cytotoxic T lymphocytes"(CTL),"natural k i l l e r cells"(NK) and activated macrophages". Thus lentinan exerts ~ugmentation of tumor specific and non-specific, but selective effector cells induction. Lentinan triogers increased production of "Interleukin l " ( I L l ) by direct impact on macrophages (M~) or indirectly by augmented colony stimulating factor (CSF) production from lentinan stimulated T cells. Thus increased production of ILl results in augmented maturation of premature lymphoid cells into mature cells capable to differentiate into effector cells, resulting in the formation of amplification loop to induce IL2 responder and producer mature T cells. In nu/nu this amplification loop may not function. In actual, serum factors functioning to augment the reactivity of precursor cells to lymphokines were detected only in nu/~ intact in immunocompetent T cell compartment. The proposed mode of action well explains characteristics of antitumor action of lentinan. ANTIVIRAL AND ANTITUMOR ACTIVITIES INDUCED BY LENTINAN AND THEIR POSSIBLE MEO4ANISMS
78
Kenneth S. S. Chang Viral Oncogenesis Section, Lab. of Cell Biology, NCI, NIH, Bethesda, MD. 2020S, USA Lentinan, a glucan derived from fruit bodies or mycelia of basidiomycet~s, Lentinus edodes (Berk) Sing., was tested for its antiviral and antitumor activities in mice. Daily i.p. injections of lentinan in mice postinfection afforded a significant degree of protection against encephalitis caused by the intranasally infected vesicular stomatitis virus. Pretreatment in addition to postinfection treatment was more effective than the latter alone. Lentinan treatment also markedly improved the survival of CF-I mice transplanted with allogeneic trophoblastic tumor cells which lacked H-2 antigen expression and are insusceptible to alloiwanune T cells. The natural killer (NK) cell activity, to which the trophoblast cells are fully susceptible, was markedly enhanced by lentinan. Although daily post-transplantation treatment with lentinan showed no protection of BALB/c mice against transplanted sFngeneic Abelson tumor, I0 daily injections of lentinan after an immunizing dose of Abelson virus have potentiated its immunizing capacity, resulting in a significant reduction in the size of tumor developing after Abelson tumor challenge. In addition to its potentiating effect on macrophages, and T and NK cells, lentinan may activate target spleen cells for Abelson virus replication and transformation, so that enhanced antigenic stimulation of the host is effected.
GLUCANS II AUGMENTATION OF INTERLEUKIN l PRODUCTION BY ANTITUMOR POLYSACCHARIDE, LENTINAN AND ITS ROLES IN THE GENERATION OF EFFECTOR T CELLS AGAINST TUMORS
I R.Yoshimoto,ly.Akiyan~,2T.Hayami,ly.Iguchi,lM.Izawa and 1j.Hamuro2
Central Research Laboratories, Ajinomoto Co., Inc., Yokohama and Research Laboratories Morishita Pharmaceutical Co. Ltd., Yasu-cho, Shiga, Japan.
The production by lentinan(LNT) of interleukin l ( I L l ) was investigated in detail. Both of peritoneal adherent cells(PC) harvested from LNT treated mice induced augmented ILl production, showingapeak augmentation on day3. Similarly, significant augmentation of ILl production by LNT was observed when PC was co-cultured in vitro withRcritical concentration of LNT in 48hrs. PC deleted of T cells(anti-Thyl+C') and macrophage cell line P388Dl induced augmented production of ILl when co-cultured with LNT. Thus LNT acts on macrophages (MB) directly to augment the production of ILl. Colony stimulating factor(s)(CSF) produced from LNT stimulated T cells also augmented the production of ILl from M~. Therefore LNT triggers increased production of ILl by direct impact on M~ or indirectly via augmented CSF production from LNT stimulated T cells synergistically. To evaluate the role of this augmented production of ILl by LNT, generation of a l l o k i l l e r cells from thymocytes was investigated. As anticipated, thymocytes harvested from responder mice treated with LNT induced augmented generation of all o k i l l e r cells in the presence of IL2 during 5day MLC. In conclusion, LNT promotes differentiation of premature T cells into immunocompetent ~ture T cells in periphery via ILl production.
61