Showing papers by "Takashi Saito published in 1996"

Interferon gamma production by natural killer (NK) cells and NK1.1+ T cells upon NKR-P1 cross-linking.

Abstract: Natural killer (NK) cells play an important role in immune response by producing interferon gamma (IFN-gamma) as well as exhibiting cytotoxic function. IFN-gamma produced by NK cells has been suggested to be involved in differentiation of T helper cells. On the other hand, the NKR-P1 molecule was recently identified as one of the important NK cell receptors, and it recognizes certain kinds of oligosaccharides on target cells and triggers NK cells for cytotoxicity. In the present study, we found that NK cells produce great amounts of IFN-gamma upon cross-linking of the NKR-P1 molecule. In contrast, stimulation of NK cells with IL-2 induced proliferation without producing IFN-gamma. Similar to NK cells, NK1.1+ T cells also produced IFN-gamma upon NKR-P1 cross-linking. NK1.1+ T cells produced IFN-gamma but not interleukin 4 (IL-4) upon NKR-P1 cross-linking, whereas they secreted both IFN-gamma and IL-4 upon T cell receptor cross-linking. These results indicate that NKR-P1 is a receptor molecule on NK and NK1.1+ T cells that induces not only cytotoxicity but also IFN-gamma production. Our findings provide a new pathway for IFN-gamma production by NK and NK1.1+ T cells through NKR-P1 molecules; it may be essential for immune regulation.

Oxidative stress by tumor-derived macrophages suppresses the expression of CD3 ζ chain of T-cell receptor complex and antigen-specific T-cell responses

Abstract: One of the important mechanisms of immunosuppression in the tumor-bearing status has been attributed to the down-modulation of the CD3 zeta chain and its associated signaling molecules in T cells. Thus, the mechanism of the disappearance of CD3 zeta was investigated in tumor-bearing mice (TBM). The decrease of CD3 zeta was observed both in the cell lysate and intact cells. Direct interaction of T cells with macrophages from TBM (TBM-macrophages) induced the decrease of CD3 zeta, and depletion of macrophages rapidly restored the CD3 zeta expression. We found that treatment of such macrophages with N-acetylcysteine, known as antioxidant compound, prevented the decrease of CD3 zeta. Consistent with this result, the addition of oxidative reagents such as hydrogen peroxide and diamide induced the decrease of CD3 zeta expression in T cells. Consequently, the loss of CD3 zeta resulted in suppression of the antigen-specific T-cell response. These results demonstrate that oxidative stress by macrophages in tumor-bearing status induces abnormality of the T-cell receptor complex by cell interactions with T cells. Therefore, our findings suggest that oxidative stress contributes to the regulation of the expression and function of the T-cell receptor complex.

Inactivation of human immunodeficiency virus (HIV)-1 envelope-specific CD8+ cytotoxic T lymphocytes by free antigenic peptide: A self-veto mechanism?

Abstract: Free peptide has been found to inhibit cytotoxic T lymphocyte (CTL) activity, and veto cells bearing peptide-major histocompatibility complex (MHC) complexes have been found to inactivate CTL, but the two phenomena have not been connected. Here we show that a common mechanism may apply to both. CD8+ CTL lines or clones specific for a determinant of the human immunodeficiency virus (HIV) 1 IIIB envelope protein gp160, P18IIIB, are inhibited by as little as 10 min exposure to the minimal 10-mer peptide, I-10, within P18IIIB, free in solution, in contrast to peptide already bound to antigen-presenting cells (APC), which does not inhibit. Several lines of evidence suggest that the peptide must be processed and presented by H-2Dd on the CTL itself to the specific T cell receptor (TCR) to be inhibitory. The inhibition was not killing, in that CTL did not kill 51Cr-labeled sister CTL in the presence of free peptide, and in mixing experiments with CTL lines of different specificities restricted by the same MHC molecule, Dd, the presence of free peptide recognized by one CTL line did not inhibit the activity of the other CTL line that could present the peptide. Also, partial recovery of activity could be elicited by restimulation with cell-bound peptide, supporting the conclusion that neither fratricide nor suicide (apoptosis) was involved. The classic veto phenomenon was ruled out by failure of peptide-bearing CTL to inactivate others. Using pairs of CTL lines of differing specificity but similar MHC restriction, each pulsed with the peptide for which the other is specific, we showed that the minimal requirement is simultaneous engagement of the TCR and class I MHC molecules of the same cell. This could occur in single cells or pairs of cells presenting peptide to each other. Thus, mechanistically, the inhibition is analogous to veto, and might be called self-veto. As a clue to a possible mechanism, we found that free I-10 peptide induced apparent downregulation of expression of specific TCR as well as interleukin 2 receptor, CD69, lymphocyte function-associated antigen 1, and CD8. This self-veto effect also has implications for in vivo immunization and mechanisms of viral escape from CTL immunity.

Site-directed mutagenesis of hamster complement C1S: Characterization with an active form-specific antibody and possible involvement of C1S in tumorigenicity

Abstract: We have previously shown that non-transformed mouse A31 cells became tumorigenic when they were transfected with hamster C1s cDNA expression plasmid BCMGSNeoCS. In the present study, mutations were introduced into the cDNA at the activation cleavage site, Arg423(AGG) and the active center Ser617(AGC). These amino-acids were replaced by His423(CAC) and Thr617(ACC), respectively. The mutated cDNAs were inserted into BCMGSNeo and transfected to A31 and its polyoma-virus-transformed SEA7 cells. C1s produced from these transfectants lost their enzyme activity. Transfectants of these mutated C1s cDNA did not form tumors in nude mice, To distinguish between active and inactive C1s in situ, we have developed novel antibodies, one directed to the NH2-terminal neoepitope of the L chain and the other specific for uncleaved inactive C1s. These antibodies were used to characterize C1s produced by transfectants, so as to determine whether or not it was cleaved at the right position.

Registration accuracy measurement mark

Abstract: The present invention includes a first semiconductor element forming member formed in a first layer, a first measurement mark formed by the same manufacturing step as the first semiconductor element forming member, a second semiconductor element forming member formed in a second layer above the first layer, and a second measurement mark formed in the same manufacturing step as the second semiconductor element forming member for measuring registration accuracy between the first and second semiconductor element forming members. The first measurement mark has a pattern which receives same influence of aberration as the first semiconductor element forming member when irradiated with light, and the second measurement mark has a pattern which receives same influence of aberration as the second semiconductor element forming member when irradiated with light. Thus, a registration accuracy measurement mark taking into consideration the influence of aberration can be provided.

Stabilizer for chlorine-containing polymer, preparation thereof, and chlorine-containing polymer composition

Abstract: PURPOSE: To provide a stabilizer, for a chlorine-contg. polymer, which is excellent in incorporation into a chlorine-contg. polymer and thermal stability and has a suppressed water-condensing property. CONSTITUTION: A compsn. comprising a silicic compd., selected from the group consisting of silicic acid, a salt of silicic acid, a salt of aluminosilicic acid and an acid-treated product thereof, and contg. a reactive silicic acid, and a fat and oil mixed and reacted with at least one member selected from the group consisting of an oxide, a hydroxide, and a reactive salt of the group II, IV and/or V metals of the periodic table in an amount of not less than the total amt. of the stoichiometric amount of KOH for the saponification of the fat and oil and the amount of KOH necessary for the neutralization of the reactive silicic acid in the presence of water to convert the reactive silicic acid to a silicate of the group II, IV and/or V metals and, at the same time, to carry the saponification product on the silicic compd.

Method for dissolving and isolating gaseous carbon dioxide under sea and device therefor

Abstract: PURPOSE: To provide a simple and efficient means for dissolving the gaseous carbon dioxide discharged from a thermal power plant, etc., under the sea and isolating the carbon dioxide in a deep sea. CONSTITUTION: A short-leg gas-lift dissolving pipe 2 and a long-leg settling pipe 3 are connected at the upper part to form a gas lift 1 in the shape of an inverted U, the dissolving pipe 2 is held in a shallow sea, and the lower end of the settling pipe 3 is opened in a deep sea. Gaseous carbon dioxide is blown in from the lower end of the dissolving pipe 2, the seawater is allowed to flow in from the lower end by the gas lifting action of the carbon dioxide in the dissolving pipe 2, and the carbon dioxide is completely dissolved until the carbon dioxide reaches the upper end of the dissolving pipe. The seawater with the density increased by the dissolved carbon dioxide is settled into the deep sea by gravity flow through the settling pipe 3.

Effect of recombinant human granulocyte colony-stimulating factor on combination therapy with aztreonam and clindamycin for infections in neutropenic patients with hematologic diseases.

Abstract: The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases. Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day). The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group). The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group. Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same. These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.

Compatibility precision measurement mark for semiconductor photomask manufacture

Abstract: The precision mark has a semiconductor device imaging region, a compatibility precision measurement mark production region, and two semiconductor element production parts. Provided in the device production region are several layers of patterns which form a semiconductor element having a predetermined shape on a semiconductor substrate (1). The two semiconductor element production parts are provided in respective semiconductor layers of the semiconductor production region, one above the other. Provided in the same respective production steps as the two semiconductor elements are respective reference marks (100,200). The latter mark (200) measures compatibility precision between the two semiconductor production parts. The two reference marks are in the form of patterns which are influenced by exposure to the same abberations as their respective production parts when they are exposed by light.