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Biomedical subjects

G Suzuki

Publications and source records attributed to G Suzuki.

At least 127 records · Page 7Linked to original sources
PubMed1988

Induction of anomalous killing activity from antigen-specific CTL clones by adding high doses of human recombinant interleukin 2.

Four out of six long-term murine cytotoxic T lymphocyte (CTL) clones specific for trinitrophenyl (TNP)-modified spleen cells could develop an anomalous cytotoxicity against syngeneic and allogeneic tumor cells upon stimulation with TNP-modified spleen cells and high doses of human recombinant interleukin 2 (rIL-2). On FACS analysis, hyperactivated CTLs were positive for Thy-1, Ly 2 and LFA-1, but negative for L3T4 and asialo GM1. The staining profile of the cells with each antibody indicated that the CTL clones consisted of just one cell type. Monoclonal anti-Ly 2.2 and anti-LAA (lymphokine-activated cell-associated antigen) antibodies inhibited cytolysis of CTL and hyperactivated CTL clones against TNP-modified spleen cells, but failed to inhibit the anomalous killing of the hyperactivated CTL. The cold target competition test suggested the degeneracy of antigen specificity. The present study demonstrated that the CTL clone acquired a new specificity for tumor target cells upon stimulation with a high dose of rIL-2.

Animals↗
PubMed1987

Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation.

The present study shows the in vitro effects of a novel immunosuppressive agent, FK506, in comparison with cyclosporin A (CsA). FK506 inhibited concanavalin A response and allo-mixed lymphocyte reaction of murine splenic lymphocytes in a dose-dependent manner, and at 40- to 200-fold lower concentrations than CsA. Allo-cytolytic T lymphocyte induction from murine thymocytes was also inhibited by FK506, whereas the ability of cytolytic T lymphocyte to lyse targets was not affected by the agent. Immunosuppressive effects of FK506 were further characterized by using antigen specific-proliferative T lymphocyte clones, BC.21 and KO.6. FK506 inhibited the proliferation of T cell clones stimulated with specific antigens in a dose-dependent manner, and at about 100-fold lower concentrations than CsA. However, cloned T cells, once activated, were scarcely affected by the agent; interleukin-2 (IL-2) driven proliferation of cloned T cells was not inhibited. On the other hand, it was found that FK506 inhibited both IL-2 secretion and IL-2 receptor expression of BC.21 after stimulation with the specific antigen. FK506 also inhibited the proliferation of BC.21 stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore, indicating that it directly affected the signaling pathway downward from the perturbation of the Ti/T3 complex. Finally, it was suggested that FK506 and CsA synergistically inhibited the antigen-driven proliferation of cloned T cells. These results indicate that the novel immunosuppressive agent, FK506, affects T cell activation with mechanisms similar to those of CsA but at considerably lower concentrations.

Animals↗
PubMed1987

Signals for activation and proliferation of murine T lymphocyte clones.

Biochemical signals required for the growth of T cell clones were studied. Antigen-specific helper T cell clones, 6-1 and KO.6, could enter the state similar to the resting state where the cells expressed only small numbers of interleukin 2 (IL2) receptors and could not respond to IL2 without antigenic stimulation. A combination of a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), and a calcium ionophore, A23187, induced the expression of IL2 receptors on resting 6-1 cells and induced DNA synthesis in the presence of IL2. TPA alone did not induce IL2 receptors. A23187 induced the expression of the receptors to some extent but did not induce DNA synthesis even in the presence of IL2. IL2 receptors induced by A23187 alone were mostly low affinity receptors, whereas the combination of TPA and A23187 induced high affinity receptors in addition to low affinity receptors. Resting KO.6 cells produced IL2 in response to a combination of TPA and A23187, whereas either one of the agents did not induce the production of IL2. Dicaprylin, a permeable diacylglycerol and a potent activator of protein kinase C (the Ca2+/phospholipid-dependent enzyme) could replace TPA in both cases when dicaprylin was repeatedly added to the culture. These results suggest that strong and continuous activation of protein kinase C together with calcium mobilization is required for IL2 production and IL2 receptor expression. On the contrary, signals for DNA synthesis generated by binding of IL2 to IL2 receptors are different from those for IL2 production and IL2 receptor expression, as the combination of TPA and A23187 could not induce DNA synthesis without IL2.

Animals↗
PubMed1987

Establishment of interleukin 2 dependent cytotoxic T lymphocyte cell line specific for autologous brain tumor and its intracranial administration for therapy of the tumor.

Autologous brain tumor specific CTLs were induced from the patient's PBL by a mixed lymphocyte-tumor culture, and were maintained for more than 2 months in a medium containing exogenous IL-2. The autologous T cell line containing specific CTL was administered into the tumor-bed for the treatment of malignant glioma. In 2 cases out of 5, tumors regressed more than 50% in diameter. One of these patients is still alive now with full of his social activities, and it is 104 weeks after the initiation of the immunotherapy. Autologous T cell lines were safely administered in all cases without any complications nor toxicities.

Adolescent↗
PubMed1986

The pigeon cytochrome c-specific T cell response of low responder mice. I. Identification of antigenic determinants on fragment 1 to 65.

An examination of the proliferative response to pigeon cytochrome c fragments 1 to 65 and 1 to 80 by T cells from mice that are low responders to the native molecule revealed that some of the strains could respond to antigenic determinants on these fragments. T cell clones derived from B10.A(3R) and B10.A(4R) mice were used to characterize the antigenic determinants on fragment 1 to 65. All of the clones recognized syngeneic A beta:A alpha Ia molecules as their restriction element. Three B10.A(3R) clones and six B10.A(4R) clones recognized fragment 39 to 65. Another four B10.A(4R) clones responded to fragment 1 to 38. By stimulating with a series of cytochrome c fragments from different species, as well as a synthetic peptide, it was possible to localize the antigenic determinant(s) recognized by the B10.A(3R) clones to residues 45 to 58. Each clone showed a unique pattern of responsiveness to the various fragments, suggesting a diversity of T cell receptors specific for the same peptide. One B10.A(3R) clone could be stimulated by many of the 1 to 65 fragments in association with allogeneic B10.SM presenting cells and by tuna fragment 1 to 65 in association with B10.M presenting cells, although the rank order of potency for several of the fragments was different than that observed with syngeneic antigen-presenting cells. In addition, the clone was poorly reactive to a synthetic peptide containing a conservative substitution, serine for threonine, at position 49. The implications of these results for subsite dissection (agretope and epitope) of the antigenic determinant recognized by this clone are discussed.

Amino Acid Sequence↗
PubMed1985

"Exon-shuffling" maps control of antibody- and T-cell-recognition sites to the NH2-terminal domain of the class II major histocompatibility polypeptide A beta.

To investigate the role of the highly polymorphic amino-terminal (beta 1) domain of the class II major histocompatibility polypeptide A beta during recognition by T cells and antibodies, "exon-shuffling" was carried out between genomic recombinant DNA clones of Ak beta and Ad beta to generate a hybrid gene containing Ak beta exons for the amino-terminal domain followed by the Ad beta exons for the remainder of the molecule. L-cell gene transfectants expressing this hybrid A beta gene in combination with Ak alpha were compared to L cells expressing wild-type Ak beta Ak alpha dimers in tests of antigen-presentation to T-cell clones and hybridomas and for staining by a panel of anti-I-Ak-specific monoclonal antibodies. These antibodies were also tested for their reactivity with a B-lymphoma transfectant expressing Ak beta in the absence of Ak alpha. The results showed no qualitative differences in either T-cell or antibody-mediated recognition of I-Ak molecules containing either the exon-shuffled or wildtype Ak beta. Together with the data involving the B cell transfectant expressing only Ak beta, these results map control of the A beta contribution to the immunologically relevant determinants of I-Ak to the highly polymorphic amino-terminal domain and indicate little, if any, contribution to allele-specific recognition by amino acid sequence variations in the remaining portions of the A beta polypeptide.

Alleles↗
PubMed1984

Immunosuppressive activity of sera from gastric cancer patients.

Sera from 60 gastric cancer patients and 20 patients with benign gastric diseases and 8 healthy controls were tested for inhibitory effects on the humoral response to sheep erythrocytes (SRBC) by the plaque forming cell assay (PFC R.I.) using mouse spleen cells and on the phytohemagglutinin (PHA)-induced blastogenesis of normal mouse spleen cells (PHA S.R.). Gastric cancer patient sera showed a significantly lower PFC R.I. than did sera from benign gastric disease patients and from the healthy controls. However, there was no appreciable interstage difference in the degree of depression. The PHA-induced blastogenesis of normal spleen cells was also decreased in the presence of sera from cancer patients, as compared to that in the presence of sera from benign disease patients and from the healthy controls. The depression progressed with advancing stage of cancer. The PHA S.R. showed significant negative correlations with serum levels of IAP, IS, alpha 1-acid glycoprotein and alpha 1-antitrypsin, but there were no such correlations between PFC R.I. and these glycoproteins in serum. There was also no correlation between the values of the PHA S.R. and the PFC R.I. These results suggest that these two assays may depict immunosuppressive activities operating through entirely different mechanisms.

Animals↗
PubMed1984

[Endoscopic preoperative intralesional injection of OK-432 in early gastric cancer].

The study group consisted of 35 patients with early gastric cancer, 16 of whom were admitted for preoperative immunotherapy. Ten to 40 K.E. of OK-432 was injected intralesionally by endoscope, and then gastrectomy was performed. After the intralesional injection, fever, nausea, vomiting and epigastralgia occurred. In cancer lesion and regional lymph node, histological findings from OK-432 treated group were compared to those of the control group. Lymphoid cell infiltration at cancer lesion was marked in OK-432 treated group, and degenerated cancer cells were found in 3 cases. On the other hand, lymphoid follicles showed a marked statistical increase in OK-432 treated group. Also the cases with marked lymphoid follicle showed increased numbers of peripheral blood lymphocyte. From the results, intralesional injection of OK-432 may confirm the tumor-associated antigenicity and serves as a useful method to potentiate the specific and/or non-specific immunity in regional lymph nodes.

Adult↗
PubMed1983

Idiotypic and fine specificity analysis of a (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific suppressor T cell hybridoma at the level of cell surface structures, isolated receptor material and functional suppressor factor.

The (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific T suppressor cell hybridoma 7C3-13 was established by fusing splenic B10.BR T cells enriched on NP-coated petri dishes with the AKR thymoma BW5147. 7C3-13 was selected by anti-NPb idiotypic and anti-I-Jk antibodies in microcytotoxicity tests. The hybridoma expressed H-2k, I-Jk, Qa-1, Thy-1.1 as well as idiotypic (binding site-related) and framework Ig VH determinants, while it was negative for I-A, I-E/C, Thy-1.2, Lyt-1, Lyt-2 and Ig constant region determinants. Hapten-binding receptor material could be isolated from 7C3-13 cells on NP-coupled nylon nets and functionally active T suppressor factor (TsF) could be extracted from the hybridoma. Both types of soluble molecules express NPb idiotype, but the TsF carries I-J determinants in addition while the isolated receptors do not. The molecular weight of the isolated receptor material is 80 000, that of the TsF activity is 27 000 and 57 000-64 000, respectively. We thus were able to show that NP-binding molecules can be obtained in the form of cellular surface receptors, isolated receptor material and extracted TsF from one and the same, monoclonal, cell source.

Animals↗