Adoptive immunotherapy against a local or widespread tumor of a highly malignant and poorly immunogenic mouse leukemia L1210.
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Animals↗
Biomedical subjects
I Nakashima
Publications and source records attributed to I Nakashima.
Depression of afferent arc of the in vivo cytotoxic T-cell immunity by bacterial lipopolysaccharides.
The afferent arc of the in vivo cytotoxic T-cell immunity assessed by second set rejection of ascitic allogeneic tumors was shown to be depressed by bacterial lipopolysaccharide (LPS) that was administered simultaneously with or 1 day before injection of allogeneic spleen cells as stimulators. Two different LPSs from Escherichia coli O55 and Klebsiella O3 displayed similar activities whereas dextran sulfate, concanavalin A, or poly A:U was not effective. Stimulator activities of allogeneic cells was not directly modified by LPS. Any definite suppressor activity on afferent or efferent arc of the T-cell response was not demonstrable in mice receiving LPS and allogeneic cells. Further, the LPS effect for immune depression was not diminished by whole body X-ray irradiation to the recipient at 300 R, which ablated the B-cell reactivity to LPS for polyclonal activation, or by treatment of the recipient with carrageenan, a known toxic agent to macrophages. It was suggested from these results that LPS suppresses the cytotoxic T-cell immunity by modulating responder T cells to be temporarily refractory to the allogeneic stimulus rather than by activating suppressor cells such as radiation-sensitive lymphocytes and carrageenan-sensitive macrophages.
Animals↗
Human IgE antibody to the carbohydrate-containing third domain of chicken ovomucoid.
Two kinds of the third domain, either with or without a carbohydrate chain, were prepared from chicken ovomucoid. The immunoreactivity of the domain preparations to human IgE antibody directed against ovomucoid was examined by using the sera from patients of egg allergy. About 30% of the serum antibody to ovomucoid reacted with the carbohydrate-containing domain, whereas little or no antibody with reactivity to the carbohydrate-free domain was detected, suggesting that the carbohydrate chain attached to the third domain played an important role in antigenic determinants of the carbohydrate-containing third domain against the human IgE antibody.
Animals↗
Genetic and stimulatory cell type requirements for inducing class I major histocompatibility complex alloantigen-specific in vivo cytotoxic T cell immunity.
Current interpretation based on analytical in vitro works that actions of Ia antigens and accessory cells such as macrophages and dendritic cells are crucial for inducing cytotoxic T cell responses to class I major histocompatibility complex (MHC) alloantigens has been challenged by experiments performed in a newly developed system handling in vivo cytotoxic T cell immunity. We first characterized the transplantation immunity for second-set rejection of ascitic tumor allografts as principally induced by allogeneic stimulator cells via direct pathway, and as exclusively mediated by class I MHC alloantigen-specific in vivo cytotoxic T cell activity. By comparison of activities of limiting effective doses (10(4)-10(5) cells per mouse) of various stimulator cells in this defined system, we could demonstrate that genetic disparity at the D region of H-2 to the recipient is just enough for inducing the immunity, and presence of allogeneic or syngeneic Ia antigens in addition to H-2D alloantigens on stimulator cells does not give any premium effect. Further study revealed that allogeneic peritoneal cells rich in macrophages or glass-adherent spleen cells enriched for dendritic cells are not stronger stimulators than allogeneic adherent cell-depleted spleen cells and semi-allogeneic thymocytes. These results fit with the alternative concept that the physiological pathway inducing in vivo cytotoxic T cell immunity for graft rejection entirely depends on class I MHC antigens on live lymphocytes as self-supported stimulators, and does not crucially involve additional stimulator activities of Ia antigens and special accessory cell types, which must be in vivo concerned with induction of other types of transplantation immunity.
Animals↗
Potent adjuvant action of lipopolysaccharides possessing the O-specific polysaccharide moieties consisting of mannans in antibody response against protein antigen.
It was previously reported that Klebsiella O3 lipopolysaccharide (LPS) exhibits extraordinarily strong adjuvant activity in augmenting antibody response against protein antigens in mice compared with other kinds of LPS, for example, LPS from Escherichia coli O55, O111, and O127 and Salmonella enteritidis. The present study was undertaken to clarify the relationship between the strong adjuvant activity in augmenting antibody response against deaggregated bovine gammaglobulin and the chemical structure of LPS. Among LPS from Klebsiella O1, O4, O5, and O7, only O5 LPS exhibited nearly the same degree of the strong adjuvant activity as did O3 LPS. The adjuvant activity of the other LPS was very weak in a degree similar to that of LPS from E. coli O55 and O127. Even when the natural forms of Klebsiella O3 LPS and O1 LPS were converted to various defined uniform salt forms, their adjuvant activity did not significantly differ from that of the respective natural forms. It is therefore unlikely that the difference in strength of the adjuvant activity between Klebsiella O3 LPS and O1 LPS is due to the difference in their salt forms. The common feature in the structures of Klebsiella O3 LPS and O5 LPS is their O-specific polysaccharide chains consisting of the mannose homopolysaccharides (mannans). LPS from E. coli O8 and O9, the O-specific polysaccharide chains of which consist of the mannans, also exhibited much stronger adjuvant activity than do LPS from E. coli O55 and O127, and the strength of the adjuvant activities of the former two was comparable to that of LPS from Klebsiella O3 and O5. On the other hand, LPS from Klebsiella O3 and O5 and E. coli O8 and O9 showed the ability to activate B lymphocytes polyclonally in vivo in a degree similar to that of the other kinds of LPS. From the present results it can be concluded that LPS possessing the O-specific polysaccharide moieties consisting of the mannans exhibit extraordinarily strong adjuvant activity in augmenting antibody response against protein antigen.
Adjuvants, Immunologic↗
Adjuvant actions of polyclonal lymphocyte activators. V. Proliferation of macrophage colony-forming cells in the draining lymph node.
We investigated the action of various polyclonal lymphocyte activators (PLA) on the proliferation of macrophage colony-forming cells in vivo at the local site. As PLA, Klebsiella pneumoniae 03 lipopolysaccharide (K03 LPS), Escherichia coli 0111 lipopolysaccharide (E. coli LPS), dextran sulfate (DS), concanavalin A (Con A), phytohemaggulutinin (PHA), polyadenylic-polyuridylic acid (poly(A:U], polyinosinic-polycytidylic acid (poly(I:C], and pokeweed mitogen (PWM) were used. All PLA tested acted to proliferate macrophage colony-forming cells in the draining lymph node at a late stage after subcutaneous injection. The order of strength of this action of PLA was K03 LPS greater than E. coli LPS greater than Con A greater than DS greater than PHA, PWM, poly(I:C), and poly(A:U), which corresponded to the order of strength of their adjuvant action in initiating helper-T-cell response to subcutaneous injection of aggregate-free bovine gamma-globulin. The detailed relationship between the proliferation of macrophage colony-forming cells and the adjuvant action of PLA is discussed.
Adjuvants, Immunologic↗
Simultaneous development of humoral and cellular tumor-specific immunity against L1210 mouse leukemia.
We have recently described that a variant of L1210 leukemia cell (L1210/LN-1) originally fused with Lesch-Nyhan fibroblast is highly immunogenic for inducing tumor-specific transplantation immunity in (BALB/cxDBA/2)F1 mice. This finding has clearly been confirmed in the present study by in-vitro cell-mediated cytotoxicity assay. Direct cytotoxic tests and competitive inhibition tests using tumor cells such as P388, LS-1 and L5178Y as target or inhibitor cells showed that the cell-mediated immunity is specific to L1210 leukemia. In the process of this study, we found that the CD2F1 mice hyperimmune to L1210 leukemia cells developed co-existing humoral anti-L1210 leukemia immunity. In an in vitro complement-dependent cytotoxicity test and absorption test, antisera from hyperimmune mice reacted specifically to L1210 leukemia cells, but not other tumor cells such as P388, L5178Y, LS-1, DB27C and BW5147 or normal cells from various tissues of DBA/2, BALB/c and AKR mice. In an in vitro cytotoxicity blocking test, the cytotoxic antisera specifically reactive to L1210 cells totally failed to inhibit lysis of L1210 cells by cytotoxic cells, suggesting that antigens recognized by cell-mediated cytotoxicity assays are not identical to serologically defined tumor-cell surface antigens.
Animals↗
Ontogeny of the transplantation immunity of mice for rejecting ascitic allogeneic tumors.
Ontogeny of the murine transplantation immunity for rejecting ascitic allogeneic tumors (chemically-induced RG lymphoma and L1210 leukemia) as a model of in vivo cytotoxic T cell immunity was studied. Challenge by 10(6) to 10(7) allogeneic tumor cells per 20 g body weight (b.w.) of the mouse was fatal to 1-3 day-old mice, whereas 7-30 day-old mice rejected the tumor. In newborn mice however some yet undetermined mechanism worked to temporally depress the initial tumor growth. Injection of low (10(6) cells per 20 g b.w.) to moderate (10(7)) doses of semiallogeneic spleen cells into newborn mice prepared for second set rejection of the tumor carrying the same alloantigens as the spleen cells, although injection of high dose (3 X 10(8)) cells reduced the tumor rejecting immunity. This second set rejection occurred even against the allogeneic tumor inoculated as early as 3 days old, if the mice had been primed with the alloantigens at birth. It appears therefore that newborn and early suckling mice are protected from tumor invasion by cytotoxic immunity more powerfully than expected from earlier in vitro works.
Age Factors↗
Immune reactivity of allogeneically pregnant mice to paternal MHC antigens on fetal and placental cells assessed by second set rejection of ascites tumor cells.
In vivo immunogenicity of fetus- and placenta-derived cells as well as the immune reactivity of pregnant mice to fetal cells were examined for graft rejecting response (GRR). Systemic administration of small numbers of fetal cells but not placental cells from allogeneically pregnant mice (10(6) cells per mouse) or adult allogeneic spleen cells (10(4) cells) sensitized mice for second-set rejection of an ascitic tumor bearing paternal major histocompatibility complex (MHC) antigens. Despite this fact and the known positive humoral response, pregnant and parous mice are not even minimally sensitized with fetal MHC antigens for GRR transplacentally. Nevertheless, any pregnancy-related systemically active control, which would selectively prevent the mother from being sensitized for GRR by limiting numbers of semi-allogeneic fetal cells, was not demonstrable in either allogeneically or syngeneically pregnant mice. Irrespective of pregnancy, mice did not, however, respond to repeated administration of very small numbers of allogeneic spleen cells (5 X 10(2) cells per mouse) for graft rejection. These findings support the notion that deviation of maternal immunity to fetal antigens away from harmful GRR is mediated principally by local mechanisms which inhibit fetal cells from gaining access to the mother for GRR, and additionally by the innate inability of mice to respond to very small numbers of allogeneic cells that might escape past the local maternal-fetal barrier.
Animals↗
Direct activation of Sendai virus (HVJ)-specific cell-mediated immunity of mice for second set rejection of the virus-infected syngeneic tumor by noninfectious virus-sensitized spleen cells.
Syngeneic spleen cells (SPC) sensitized in vitro with noninfectious NVJ were shown to effectively stimulate mice to generate the HVJ-specific cell-mediated immunity for second set rejection (SSR) of virus-infected syngeneic leukemia cells. As few as 10(4) live but not disrupted SPC either infected with a temperature-sensitive mutant of HVJ (HVJts) or sensitized passively with ultraviolet (UV)-inactivated HVJts were active as immunogen. Syngeneic SPC as the carrier of virus could be replaced by allogeneic SPC or L cells, a fibroblast cell line, without reduction of the immunogenicity. Further study demonstrated that a special density of antigen on the surface of HVJts-sensitized SPC is required for high immunogenicity. It was suggested that live cells appropriately sensitized with noninfectious virus would serve as an excellent vaccine for virus-specific cell-mediated immunity.
Animals↗
Effects of dietary zinc deficiency on hepatic ornithine carbamoyltransferase and alcohol dehydrogenase activities in rats.
Hepatic ornithine carbamoyltransferase (OCT) and alcohol dehydrogenase (ADH) activities were measured in six groups of rats: (A) fed a severe zinc-(Zn-) deficient diet (1.98 ppm) for 5 weeks; (B) pair-fed control for group (A); (C) fed a less severe Zn-deficient diet (6.10 ppm) for 5 weeks; (D) pair-fed control for group (C); (E) fed a Zn-supplemented control diet (90.4 ppm) for 5 weeks; and (F) first fed the severe Zn-deficient diet for 5 weeks and then replaced on the Zn-supplemented control diet until a body weight corresponding to the final weight of group (E) was obtained. Hepatic OCT was similar in all these six groups. On the contrary, hepatic ADH was significantly reduced in groups (A) and (C) and in each of the corresponding pair-fed groups, (B) and (D). No differences were found between groups (A) and (B) or between groups (C) and (D). In group (F), ADH activity improved to a level equivalent to that in group (E). The changes in ADH activities were accompanied by changes in the hepatic Zn content. Thus, it is clear that: (1) the hepatic Zn content may not be affected by the amount of Zn intake alone, but by the combination of Zn and food intake; and (2) ADH, and not OCT, reflected the hepatic Zn content.
Alcohol Dehydrogenase↗
Mononuclear phagocyte colony formation of human spleen cells in liquid culture.
We found that mononuclear phagocytes formed a distinct number of clusters and colonies on the bottom of a culture dish 7 days later but granulocytes did not, when a large number of human spleen cells were cultured in liquid medium. In all gastric cancer bearers and patients with portal hypertension operated on, however, colony formation was restricted to spleen cells from patients with advanced gastric cancer and from a group of patients with portal hypertension. These spleen cells formed mononuclear phagocyte colonies without the help of exogeneous colony stimulating factor (CSF). We further demonstrated that the colony-forming cells were glass non-adherent and nylon wool adherent, and that spontaneous colony formation required cooperation between the colony-forming cells and colony-stimulating cells adherent to a plastic surface.
Cell Adhesion↗
In vivo effects of bacterial lipopolysaccharide on proliferation of macrophage colony-forming cells in bone marrow and peripheral lymphoid tissues.
Changes in the number of macrophage colony-forming cells in various tissues of mice injected with lipopolysaccharide (LPS) from Klebsiella pneumoniae, Escherichia coli, or Salmonella enteritidis were studied. The injection of LPS increased macrophage colony-forming cells in peripheral lymphoid tissues such as the spleen, mesenteric lymph nodes, and regional lymph node, although the same treatment caused the decrease of such cells in the bone marrow. This phenomenon was consistently observed when tested by various LPSs. The injection of LPS into mice which had been exposed to X-ray irradiation and reconstituted with syngeneic normal bone marrow cells decreased colony-forming cells in the spleen. The increase of macrophage colony-forming cells in the spleen seemed, therefore, not to be due to migration from the bone marrow. The injection of LPS appeared to shorten the lag time before the initiation of mitosis of colony-forming cells in the spleen but not in the bone marrow. No participation of serum factors in this phenomenon could be detected. It was suggested that there might be an essential difference between the responsiveness to LPS of macrophage colony-forming cells in the spleen and those of the bone marrow.
Animals↗
Structure of the polysaccharide moiety of the Klebsiella O3 lipopolysaccharide isolated from culture supernatant of decapsulated mutant (Klebsiella O3:K1-).
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Chemical Phenomena↗
Adjuvant actions of linear mannan-possessing lipopolysaccharide (LPS) in LPS-resistant C3H/HeJ mice.
Immunopotentiation has been demonstrated when Klebsiella O3 lipopolysaccharide (KO3 LPS), which possesses a linear mannan as the O-specific side chain, was injected subcutaneously into endotoxin resistant C3H/HeJ mice together with soluble protein antigens. The LPS exhibited significantly positive adjuvant effects on antibody responses in vivo after secondary antigen challenge and on delayed-type hypersensitivity (DTH) reactions against protein antigens. However, KO3 LPS was not a polyclonal B cell activator (PBA) in C3H/HeJ mice nor mitogenic in cultures of spleen cells of C3H/HeJ. Thus, the activity of the LPS in C3H/HeJ mice is confined to the potentiation of T-dependent immune responses. The contribution of the mannan O side chain to the adjuvant action of KO3 LPS was suggested.
Adjuvants, Immunologic↗
Strong adjuvanticity of bacterial lipopolysaccharides possessing the homopolysaccharides consisting of mannose as the O-specific polysaccharide chains.
The lipopolysaccharides (LPS) from Klebsiella 03 and 05 and Escherichia coli 08 and 09 are unique in having linear homopolysaccharides consisting of mannose as the O-specific polysaccharide chains. All four kinds of LPS were found to exhibit very strong adjuvanticity in induction of delayed-type hypersensitivity to ovalbumin in mice compared with other kinds of LPS from Klebsiella, E. coli and Salmonella. Even if the natural forms of Klebsiella 03 LPS and 01 LPS were converted to various defined uniform salt forms, their adjuvanticity did not differ significantly from that of the respective natural forms. It was concluded therefore that the difference in strength of the adjuvanticity between them is not due to the difference in their salt forms, solubility and physical state. Correspondingly, with strong adjuvanticity of Klebsiella 03 LPS and 05 LPS, their activity in enlarging the regional lymph node was also strong. Various uniform salt forms of Klebsiella 03 LPS caused stronger regional lymph node enlargement than those of Klebsiella 01 LPS. However, the activity of E. coli 08 LPS and 09 LPS in enlarging the regional lymph node was significantly weaker than that of Klebsiella 03 LPS and 05 LPS, and there were other kinds of LPS which showed a capacity to enlarge the regional lymph node similar to that of E. coli 08 LPS and 09 LPS, despite their weak adjuvanticity. Therefore, correlation did not necessarily exist between the degree of adjuvanticity of LPS and its activity in enlarging the regional lymph node.
Adjuvants, Immunologic↗
Genetic controls of T cell-independent Thy-1 alloantibody responses.
Early and late primary IgM antibody responses of mice to Thy-1.1 antigens showed different antigenic and cellular requirements. We studied genetic controls of the early primary responses, which could be induced by subcellular thymocyte antigens independently of host T-cell activity. All Thy-1.2 mouse strains of Igha (BALB/c and BC8), Igh-VaCb (BAB14), Ighd (AKR/Cum), Ighj (CBA/J, C3H/HeN, C3H.SW, and C3H.JK), and Ighn (NZB) definitely responded early to Thy-1.1 antigens from AKR/J (Ighd), A.Thy-1.1 (Ighe), or B10.Thy-1.1 (Ighb) mice or SD rats, whereas all strains of Ighb (C57BL/6, C57BL/10, B10.D2, B10.BR, B10.A, CB20 and CWB), Ighc (DBA/2), Ighe (A/J), and Igho (C.AL20) responded poorly to the same antigens. This contrasts with the observation that both strains of Ighj (C3H/HeN) and Ighb (B10.BR) responded well at later times. As was the case for late responses, the matching of H-2 between donor and recipient resulted in early responses of exceptional quality in high-responder strains. It was concluded that under the influence of H-2, whose incompatibility between donor and recipient partially interferes with responses, early but not late primary Thy-1.1-specific antibody responses are selectively controlled by Igh-V or closely linked Ir gene(s) as a new VH marker.
Animals↗
Correlation between strong adjuvanticity of Klebsiella O3 lipopolysaccharide and its ability to induce interleukin-1 secretion.
Adjuvant activity of Klebsiella O3 lipopolysaccharide (KO3 LPS) in augmenting antibody response and delayed-type hypersensitivity to protein antigens in SMA mice was much stronger than that of LPS from Escherichia coli O55 and O127 (EO55 LPS and EO127 LPS). Relationship between strength of the adjuvant activity and that of the ability to induce interleukin-1 (IL-1) secretion by peritoneal macrophages from C3H/HeN or SMA mice was investigated using these three kinds of LPS. When supernatant samples of macrophages cultured at 37 degrees C for 24 hr in the presence of 5 micrograms/ml LPS were assayed by their mitogenic effect on thymocytes from C3H/HeJ mice, KO3 LPS induced the secretion of about four to six times greater amounts of IL-1 activity than did EO127 LPS. When concentration of LPS used for stimulation of macrophages was varied from 0.1 to 50 micrograms/ml, KO3 LPS induced the secretion of definitely greater amounts of IL-1 activity than did EO55 LPS and EO127 LPS throughout the LPS concentrations tested. Nearly the same amount of IL-1 activity as that produced by 10 micrograms/ml EO55 LPS or 50 micrograms/ml EO127 LPS could be produced by 1.0 microgram/ml or lower concentrations of KO3 LPS.
Adjuvants, Immunologic↗