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Biomedical subjects

M Taniguchi

Publications and source records attributed to M Taniguchi.

At least 667 records · Page 37Linked to original sources

Acquisition of repertoires of suppressor T cells under the influence of macrophages.

Acquisition of repertoires and genetic restriction specificities of suppressor T cells (Ts) and their factors were studied by using full allogeneic radiation bone marrow chimera and H-2 congenic pairs, B10.A(3R) and B10.A(5R), which received conventional or cloned macrophages by cell transfer. Suppressor T-cell factor (TsF) from C3H----C57BL/6 or C57BL/6----C3H chimera suppressed only donor but not host-type responses of either C3H or C57BL/6, in an antigen-specific fashion. However, if chimera mice were given conventional or cloned macrophages of the host type, the chimera TsF in turn suppressed both the responses of C3H and C57BL/6 mice but not those of the third party, BALB/c, indicating that macrophages are responsible for the acquisition of host restriction specificity. Similarly, B10.A(5R) mice developed I-Jb restricted Ts or TsF when the B10.A(3R) macrophage cell line was injected at the time of antigen priming. The reverse was also true. B10.A(3R) mice did generate I-Jk restricted Ts when they received the B10.A(5R) macrophage cell line. Thus, the results clearly demonstrated that B10.A(3R) or B10.A(5R) mice potentially possessed their ability to express both I-Jk and I-Jb determinants and that repertoires and genetic restriction specificity of Ts and their TsF were acquired at a macrophage level at the time of antigen-priming.

Animals↗

Analysis of melanoma antigen and its involvement in tumor-escape mechanisms.

Melanoma antigen was characterized by using the C57BL/6 mouse melanoma (B16) system, especially in relation to escape mechanisms of tumor cells from immunological surveillance. The antigen on the surface of melanoma cells selectively induced double negative cytotoxic T lymphocytes (CTL) lacking genetic restriction specificity in their action, whereas the soluble antigen shed or secreted from the cells preferentially induced suppressor T cells (Ts) inhibiting CTL generation in the induction phase. The epitopes of melanoma antigen for CTL and Ts were found to possess a "GM3-like structure". Anti-melanoma CTL activity was blocked by either GM3(NeuAc)-or GM3(NeuGc)-liposomes. Moreover, the GM3 (NeuGc)-liposome could induce anti-melanoma CTL when used as an antigen in the in vitro primary response. On the other hand, the soluble melanoma antigen or GM3(NeuAc)-but not GM3(NeuGc)-liposome itself specifically induced anti-melanoma Ts. Therefore, anti-melanoma Ts are able to distinguish GM3 molecular species. We also found two types of T cells, C3T4+ and double negative I-J+ T cells, to be involved in this suppression. Although the primary structure of melanoma GM3 was demonstrated to be the same as that of normal GM3, syngeneic anti-melanoma GM3 monoclonal antibody (M2590) did distinguish melanoma from normal cells. Further close analysis in liposome lysis experiments using various concentrations of GM3 clearly demonstrated that M2590 anti-melanoma GM3 only reacted with GM3 at a "high" density (more than 10-12 mol%), whereas no reactivity was observed at a "low" density (less than 7.5 mol%). It is clear, therefore, that the density of GM3 with normal primary structure is important in generating melanoma antigenicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of UFT on experimental liver metastases and on the immunologic capacity of the hosts].

An experimental model is introduced for the study on liver metastasis using intrasplenically injected EL-4 and Lewis lung tumor (LLT) cells. The inhibitory effects of UFT, FT and 5-FU on the frequencies of metastatic foci in the liver were compared. All drugs showed inhibitory effect on the frequencies of liver metastasis. However, a high dose of UFT suppressed strongly the frequencies of liver metastasis. In order to compare the immunosuppressive activity of UFT with that of FT and 5-FU at the dose to give 50% inhibition of liver metastasis (MED50), we determined the MED50 values of UFT, FT or 5-FU against liver metastasis of EL-4 and LLT cells. FT and 5-FU were suppressed strongly the humoral response against SRBC, the delayed hypersensitivity against picryl chloride and the phagocytic activity. UFT had no inhibitory effect on immune responses.

Administration, Oral↗

Inhibition of tumor growth by dairy products.

Effects of dairy products (cheeses and yoghurt) on growth of transplanted murine tumors were examined in various tumor-host combinations. Suppression of tumor growth was observed in proportion to the duration of feeding. Peripheral lymph-node (LN) cells of mice fed dairy products showed an increment in the fluorescence intensity of Thy-1.2+ cells in FACS analysis. These cells showed an augmented PHA response and a remarkable antitumor effect in tumor neutralization test (Winn's assay) compared to control lymphocytes. These results suggest that dairy products enhance the activity of peripheral LN cells to suppress the tumor growth. Moreover, serum transfer from cheese fed mice revealed the protective effects against tumors, while that from yoghurt fed mice did not show such an effect. In the former mice, serum iron level was increased compared to control levels but antibody response to sheep erythrocytes (SRBC) was not augmented. From these results, we propose a hypothesis that lymphocytes may be activated by transferable serum factors such as iron-saturated transferrin and suppression of tumor growth caused by the effector-target interaction which is mediated by effector-associated transferrin in the case of cheese fed mice. In yoghurt fed mice another mechanism is suspected because of the low level of serum iron.

Animals↗

Effect of a high-fat diet on resistance to Listeria monocytogenes.

Effects of a high-fat diet on macrophage (M phi) functions were investigated. Eight-week-old ddN mice were fed a high-fat diet and carbon clearance was tested. Remarkable suppression of phagocytic activity (K16) was observed in mice fed such a diet for 1 or 2 weeks. Resistance against Listeria monocytogenes inoculated intravenously (iv) with a lethal, a sublethal, or a non-pathogenic dose was observed in the liver of mice fed a high-fat diet. When mice were infected with a lethal dose of bacteria, the number of listeria increased progressively in the liver to kill both control and a high-fat diet fed mice by day 4. The number of listeria revealed no significant difference between the group in the case of low dose inoculation. High-fat diet fed mice given a sublethal dose of bacteria showed a rise in the number of viable bacteria during the first 3 days after infection while a decline in the number of bacteria was observed in control mice during such a period. Suppression of M phi activity induced by a high-fat diet may account for the reduced resistance.

Animals↗

Density-dependent recognition of cell surface GM3 by a certain anti-melanoma antibody, and GM3 lactone as a possible immunogen: requirements for tumor-associated antigen and immunogen.

A mouse monoclonal antibody M2590, previously established after immunization of mice (C57BL/6) with syngeneic melanoma B16 cells and showing preferential reactivity with various types of melanoma over other tumor and normal cells or tissues, was shown to be directed to GM3 ganglioside. Since GM3 is widely distributed in essentially all types of animal cells, there is a conflict with the concept of a tumor-associated antigen and immunogen. Studies on the reactivity of M2590 antibody with various cells having different GM3 density at their cell surface, including cells treated with sialidase, liposomes, and solid-phase lipid layer containing different GM3 concentrations, have indicated that 1) reactivity of the antibody M2590 depends greatly on the density of GM3 exposed at the cell surface, on liposomes, or on solid phase; and 2) there is a threshold density that is recognized by the antibody in all-or-none fashion. In addition, the antibody M2590 reacts not only with GM3 but also with GM3 lactone, and the binding affinity of the antibody to GM3 lactone is strikingly higher than to GM3; however, the antibody does not react with GM3 ethyl ester. GM3 lactone was detected in melanoma as 3H-labeled GM3 gangliosidol after melanoma cells were directly treated with NaB[3H]4. A comparative immunization of BALB/c mice with GM3 and GM3 lactone showed that GM3 lactone is a much stronger immunogen than GM3, although the antibody elicited reacts with both GM3 and its lactone. Thus, the real immunogen could be GM3 lactone, although it is a minor membrane component.

Animals↗

A temperature-sensitive mutant of Abelson murine leukemia virus confers inducibility of IgM expression to transformed lymphoid cells.

Lymphoid cell lines were isolated that were inducible for the expression of surface immunoglobulin by shift from 35.5 to 39.5 degrees C after infection of mouse bone marrow cells with a mutagen-treated Abelson murine leukemia virus. Virus produced by one of the cell lines (ts49) transmitted the temperature-sensitive phenotype to new lymphoid transformants as well as to NIH/3T3 cells. In addition, the tyrosine autophosphorylating activity of the p120gag-abl protein synthesized in ts49-transformed cells was found to be temperature-sensitive. Shift experiments using ts49-transformed lymphoid cells showed that at 39.5 degrees C they synthesize increased amounts of mu and kappa chain RNA and protein, and that they can be further induced to secrete IgM when treated with lipopolysaccharide.

Abelson murine leukemia virus↗

High frequency of loss of human kappa light chain expression in mouse-human heterohybridomas.

The expression of human immunoglobulin (Ig) chains in human-mouse heterohybridomas was investigated on the days after cell fusion. Heterohybridomas were made by fusion of mediastinal lymphocytes from lung carcinoma patients and murine (BALB/c) myeloma P3U1. Most (more than 76%) of heterohybridomas easily lost the light chain rather than the heavy chain expression in the early stages after cell fusion. Frequency of loss of kappa-chain expression was predominant, whereas the expression of heavy chain and lambda-chain was rather stable in comparison with that of kappa-chain. These were also confirmed at the clonal level, demonstrating that only lambda-chain but not kappa-chain producers were successfully enriched. In fact some heterohybridomas producing human Ig of lambda-chain type established were found to be quite stable for more than 2 years without any recloning procedures.

Animals↗

Mechanism of protection during the early phase of a generalized viral infection. II. Contribution of polymorphonuclear leukocytes to protection against intravenous infection with influenza virus.

The contribution of phagocytes to the early protection of mice inoculated intravenously with influenza virus was investigated in phagocyte-depleted mice. Following the inoculation of a sublethal dose of influenza virus, virus titres in the liver and lung of both untreated and carrageenan-treated mice were reduced rapidly by day 1 and decreased slowly to reach an undetectable level by day 7. The titres in gamma-irradiated mice decreased transiently by day 1 and increased progressively thereafter to kill all of the hosts by day 8. The clearance of virus from blood at the early stage of infection was retarded by gamma-irradiation but not by carrageenan treatment. In addition, increase in virus titres in the liver and lung in the early stage of the infection was prevented by adoptive transfer with syngeneic polymorphonuclear leukocytes into gamma-irradiated mice. No significant rise of neutralizing antibody was detectable by day 3 after the inoculation, in any of the three groups of mice. These observations imply that gamma-sensitive and carrageenan-resistant polymorphonuclear leukocytes play a protective role at the early stage in the infection, whereas fixed macrophages or natural killer cells, both of which are carrageenan-sensitive and gamma-resistant, scarcely participate in the early phase.

Animals↗

Protective mechanisms against pulmonary infection with influenza virus. I. Relative contribution of polymorphonuclear leukocytes and of alveolar macrophages to protection during the early phase of intranasal infection.

The relative contribution of polymorphonuclear leukocytes and macrophages in the early protection against intranasal infection of mice with influenza virus was investigated. Virus multiplication in the lung in the early phase of infection with less than 1.5 X 10(3) plaque-forming units was enhanced by X-ray irradiation. The intranasal administration of carrageenan did not influence the titre of virus. However, when mice were infected with 1.5 X 10(4) plaque-forming units, the virus titre was elevated by intranasal administration of carrageenan as well as by X-ray irradiation, but not by intraperitoneal administration of carrageenan. The intranasal administration of carrageenan not only inhibited the phagocytic activity of alveolar macrophages but also enhanced susceptibility to the virus. On the other hand, polymorphonuclear leukocytes were capable of phagocytosing the virus in vitro and were non-permissive for virus infection. Neutralizing antibody and interferon were not detectable in the early stage of the infection. These results suggested that polymorphonuclear leukocytes (X-ray-sensitive, carrageenan-resistant) were the cells primarily responsible for early protection in influenza virus infection and that after infection with a high dose of the virus alveolar macrophages (X-ray-resistant, carrageenan-sensitive) also played a protective role in the early phase.

Administration, Intranasal↗

Specific biodetection of B16 mouse melanoma in vivo by syngeneic monoclonal antibody.

The specific detection of tumors in vivo using a radiolabeled syngeneic monoclonal antibody made by fusion of P3U1 (BALB/c myeloma cells) and C57BL/6 spleen cells primed with syngeneic B16 melanoma cells was investigated by color imaging, autoradiography, and biodistribution. The radiolabeled antimelanoma antibody specifically accumulated only in the tumor lesions, whereas no radioactivity was observed in normal tissues or organs. The distribution patterns of the radioactive antibody in the tumor lesions depended on the sizes of the tumor. Almost the entire region of the small metastatic tumor in lymph nodes was labeled, whereas the radioactive antibody was irregularly localized mainly in the center of the medium-sized tumor. However, only the peripheral region of the large primary tumor was labeled. The highest uptake of radioactivity (tumor:blood ratio) was observed in the small lymph node metastatic tumor lesions rather than in the large primary tumor. Furthermore, high resolution color imaging of B16 melanoma was also obtained by using 125I-labeled monoclonal antibody. Tumor location was specifically visible without subtraction or enhancement methods 3-5 days after injection of the radiolabeled antibody.

Animals↗

Oral immunization in adult mice to live and heat-killed Vibrio cholerae.

Effects of systemic and intestinal local immune responses in mice fed ad libitum and forcedly with live or heat-killed Vibrio cholerae on the elimination of vibrios from the intestine were investigated. In mice fed with live vibrios, ad libitum feeding could induce potential delayed-type hypersensitivity and rapid production of vibriocidal antibody in the serum whereas forcedly feeding suppressed the delayed-type hypersensitivity and retarded the antibody production. In contrast, when killed microorganisms were used as antigens, significant delayed-type hypersensitivity and rapid response of vibriocidal antibody were induced in forcedly fed mice although ad libitum feeding suppressed the induction of the delayed-type hypersensitivity and retarded the production of vibriocidal antibody. The elimination of vibrios from the intestine of mice was promoted in both mice groups fed ad libitum and forcedly with live vibrios but not with killed microorganisms. Total IgA in the intestinal contents of mice fed with live vibrios both ad libitum and forcedly were higher than those of mice fed with killed antigens. In addition, when the extracts of intestinal contents were absorbed by live antigens, IgA contents in mice fed with live vibrios were reduced more markedly than those in mice immunized orally by the feeding with killed antigens. These findings suggested that the elimination of vibrios from the organ was closely related to local IgA antibody response to heat-labile substance of live Vibrio cholerae.

Animals↗

Application and limitations of differential hybridization in the isolation of T cell-specific cDNA clones.

We investigated the limitations and effectiveness of differential hybridization in the cloning of T cell-specific cDNA (complementary DNA) molecular clones. By using the technique with T cell and B cell cDNA probes, together with Northern blot analysis, we successfully isolated cDNA clones exclusively expressed in T cells from 1 X 10(4) plaque-forming units of a T cell hybridoma. These clones represent 0.068% of the mass of the cytoplasmic mRNA. Our result shows that differential hybridization is an effective procedure when used in combination with Northern blot analysis for screening of genes selectively expressed in T cells.

Animals↗

Change in the topographical distribution of GM3 during cell spreading and growth: immunostaining with monoclonal antibody against GM3.

A monoclonal antibody, M2590, that recognizes hematoside (GM3) was used to analyze the immunostaining localization of GM3 of the surface of transformed and non-transformed hamster embryo fibroblasts and B16 melanoma cells. The reactivity of GM3 with the antibody changed markedly depending on the cell density. At the sparse density cells were clearly made visible by the antibody, but at the confluency the accessibility of the antibody to GM3 was greatly decreased. This density dependent change in the reactivity of GM3 was found for both normal and transformed cells. The staining pattern of GM3 was examined in relation to the actin fibers made visible with NBD-Phallacidin during cell spreading. When the cells were still round, the GM3 on microspikes or blebs was highly reactive with the antibody, and by the time cells showed circumferential staining of their actin fibers, GM3 had been distributed over the entire cell surface as punctuated spots. GM3 also was visible in substrate attachment materials (SAM). Trypsin treatment of SAM diminished the reactivity of GM3 with the antibody. The antibody did not inhibit cell attachment or spreading on a substratum coated with fibronectin or laminin.

Actins↗

Cholera toxin-induced tolerance to allografts in mice.

When C3H/HeN (C3H) mice were primed with viable C57BL/6 (B6) spleen cells and treated with cholera toxin (CT) on the same day, a profound tolerance to tumour allografts of B6 origin was induced. The tolerant state was sustained for as long as 6 weeks or more. Skin allografts of B6 were rejected by such tolerant C3H mice, although the survival times were prolonged very slightly. Generation of cytotoxic T lymphocytes was reduced markedly in the tolerant mice, whereas delayed footpad reaction to B6 cells was maintained at the normal immune level or higher. There is a possibility that a T-cell subset responsible for delayed footpad reaction is resistant to CT-induced tolerance and participates in the rejection of skin allografts in tolerant mice.

Animals↗