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K Yokomuro

Publications and source records attributed to K Yokomuro.

71 records · Page 4Linked to original sources
PubMed1983

Regeneration and the immune system. II. Suppressor activities of lymphocytes activated in vivo by liver regeneration and their genetic control.

The lymph node cells (LNC) activated in vivo by liver regeneration following partial hepatectomy of mice (primed lymph node cells) respond to regenerating liver cells in vitro with typical secondary immune response characteristics (Miyahara, S. et al., Eur. J. Immunol. 1983. 13: 878). These LNC activated in vivo suppress the proliferation of responder lymphocytes cultured with mitomycin C-treated regenerating syngeneic liver cells (sMLHLR). The suppressive activity was already present in LNC 4 days after partial hepatectomy and remained unchanged for at least 16 days. These primed LNC were effective not only on sMLHLR but also on syngeneic mixed lymphocyte culture (sMLR) and allogeneic mixed lymphocyte culture, of which responder cells share the I-A (I-B) subregions of the major histocompatibility complex (MHC) with primed LNC. At least one cell in the suppressor circuit is a T cell. The primed LNC restimulates in vitro with regenerating liver cells (in vitro reactivated primed LNC) suppressed the proliferation of syngeneic responder cells in sMLR, but not of cells from congeneic mice differing from the in vitro reactivated primed LNC at a cluster of genes linked to the Ig locus. Thus the suppressive activity of primed LNC is controlled by the I-A (I-B) subregions of the MHC and that of in vitro reactivated primed LNC by genes in the Ig region. The role of these suppressive cells in liver regeneration is discussed.

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PubMed1982

Regulation of immune response by preadministration of cells briefly pulsed with antigen in vitro. I. Suppression of IgE antibody response by antigen pulsed spleen cells.

The intravenous administration of syngeneic spleen cells (SPCs) briefly pulsed with antigen in vitro, results in a profound state of IgE antibody unresponsiveness. In Balb/c mice, the primary response of anti-DNP, anti-beef insulin and anti-ovalbumin IgE antibody is completely suppressed by the administration of antigen-pulsed spleen cells, 1 X 10(7), 5 X 10(7) and 1 X 10(8), respectively. This suppression is antigen specific and effects both primary and secondary immune responses. Furthermore, the immune response to dinitrophenylated Keyhole limpet hemocyanin (DNP-KLH) is most extensively suppressed by DNP-KLH pulsed SPCs, intermediately suppressed by KLH-pulsed SPCs and minimally suppressed by dinitrophenylated mouse gamma globulin or dinitrophenylated mouse serum albumin pulsed SPCs. Suppressing directly cells specific for hapten and carrier, hapten carrier protein pulsed SPCs would caused the additive suppressive effect. The suppression is induced strongly by the intravenous administration of antigen pulsed spleen cells, slightly by the subcutaneous administration and is not induced by the intravenous administration of antigen solution in phosphate buffer saline. This suppression may be mediated by either of two different mechanisms: one of them is responsible for the immediate tolerance which is induced without any suppressor cells 1 day after the administration of antigen pulsed SPCs, and the other is responsible for the suppression transferred by suppressor cells or factors to normal mice 7 days after the administration of antigen pulsed SPCs. This method in which IgE antibody response is suppressed by the administration of cells briefly pulsed in vitro with antigen, provides a powerful tool to analyze the first step of antigen specific suppression developed in vivo by conventional antigens.

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PubMed1979

Macrophage-lymphocyte interaction and genetic control of immune responsiveness.

We have reviewed briefly some of the diverse functions of macrophages in the immune response. Clearly, this population of cells interact physically with lymphoid cells, are required for activation of T cells, and process various protein antigens. Finally, we have studied the immune response to insulin in order to unify these previous data in such a way to demonstrate the active role of macrophages in the regulation of the immune response. The function of the Ir gene in the guinea pigs appears to be an intramolecular selection of discrete regions within the antigen for recognition by the T cell. The data presented suggest that this function operates at the level of the macrophage.

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PubMed1979

Partial purification, physicochemical characterization and biological function of a rosette-decreasing factor (RDF) extracted from guinea pig thymus.

A factor that decreases rosette formation between guinea pig T-cells and rabbit red blood cells (RRBC) was extracted from the thymus of the guinea pig. The active factor could be extracted from the spleen as well as the thymus, but not from the liver or kidney. The active factor of the thymic extract was found in the precipitates produced by 80% saturated ammonium sulfate and it was separated from the water-soluble fraction of the precipitates. The molecular weight of the partially purified substance was estimated to range between 10,000 and 30,000 by filtration through a diaflow membrane. From the studies on physicochemical characterization, it might be a heat-resistant basic peptide probably bound to a ribonucleotide moiety. This factor reduced rosette formation between RRBC and guinea pig T-cells, but did not reduce erythrocyte-antibody-complement rosette formation. This factor also inhibited mitogen (concanavalin A, phytohemagglutinin-P)- induced DNA synthesis of guinea pig lymphocytes and antigen-induced DNA synthesis of sensitized guinea pig lymphocytes.

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PubMed1979

Genetically restricted immune responses in guinea pigs primed in vivo with antigen-bearing macrophages.

Guinea pigs injected intradermally with antigen pulsed macrophages generate a population of immune T cells that proliferate in vitro on second exposure to antigen. T cells from F1 (2 X 13) guinea pigs immunized with DNP-OVA on one parental macrophage respond in vitro only to DNP-OVA on macrophages identical to those used for immunization and not to DNP-OVA associated with the other parental macrophages. These results demonstrate that the immunogenicity of antigen is dependent upon the macrophages used for priming in that, with this approach, strain 2 or 13 guinea pigs immunized with allogeneic macrophages pulsed with antigen do not respond to either allogeneic or syngeneic antigen-bearing macrophages. However, lysates of antigen-pulsed macrophages can still immunize either allogeneic or syngeneic recipient via their own macrophages. F1 (2 X 13) guinea pigs are immunized by insulin B chain pulsed strain 13 macrophages (responder) but not by strain 2 macrophages (nonresponder) suggesting that whether a F1 (nonresponder X responder) guinea pig recognizes antigen bound to a parental macrophage is genetically restricted before immunization to the same extent as the donor parental macrophages used for immunization.

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PubMed1978

Separation of RRBC-RFC and non-rosette forming cells (non-RFC) of guinea pig T-cell populations and their functional difference. 1. Response of RRBC-RFC and non-RFC to either Con-A or LPS.

Guinea pig lymph node cells suspension (LNC-O) was filtered through a glass wool column and the effluent (LNC-G) was further filtered through a nylon column. In this effluent (LNC-NE) about 30 per cent of the lymphocytes was identified as non-rosette forming cells (non-RFC). The non-RFC fraction was separated from LNC-NE fraction by Ficol-Conray specific gravity centrifugation or effluent cells reacted previously to rabbit red blood cells (RRBC). The upper layer after centrifugation, designated non-RFC fraction, was separated. In this fraction 96% of the cells were lymphocytes and about 95% of them were non-RFC, which lacked receptors for rabbit red blood cells (RRBC) or EAC and detectable surface immunoglobulin by conventional techniques. Though the response of the lymphocytes in the non-RFC fraction to mitogenic (Con-A, LPS) or antigenic stimulation was lower in comparison with that in RFC-rich fraction, the response of non-RFC to ConA exceeded the response to LPS. These facts suggest that at least a portion of the non-RFC may be cells from the T-cell line.

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PubMed1976

Studies on delayed-type hypersensitivity to hen egg-white lysozyme. I. Peptide fragments of lysozyme inducing delayed-type hypersensitivity.

Eleven peaks were separated by Carboxymethyl-cellulose column chromatography of peptic digest of lysozyme. Being stronger in antigenic activity two peaks of them, P-3 and P-9, were selected and purified further respectively by Amberlite IRC-50 and Sephadex G-50 column chromatography. As the results, PP-3 and PP-9 were obtained each as a single peak. For estimation of their capacities to induce delayed-type hypersensitivity, the antigen-induced 3H-thymidine incorporation, the migration inhibition of peritoneal cells and the delayed-type skin reaction were tested in guinea pigs immunized with native lysozyme or any of its fractions. PP-9 was almost as active as intact lysozyme in these capacities. On the other hand, PP-3 showed a slight inhibition of migration of peritoneal cells and no stimulation of 3H-thymidine incorporation into the lymph node cells. Moreover, the delayed-type skin reaction elicited by PP-3 was always weaker than that elicited by PP-9. Guinea pigs immunized with either PP-3 or PP-9 were also tested for these reactions. PP-9 and native lysozyme elicited these reactions in guinea pigs immunized with PP-9, but PP-3 did not. On the other hand, PP-3 and lysozyme elicited these reactions in those immunized with PP-3, but PP-9 did not. The possibility of recognition of two functionally different areas, one for production of the circulating antibody and the other for induction of delayed-type hypersensitivity, on the lysozyme molecule was discussed.

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PubMedDate not supplied

Antigen-driven clonal accumulation of peritoneal gammadelta T cells in vivo.

How the clonality of gammadelta T cells changes in response to exogenous antigens is uncertain. Here we analyzed kinetics of Vgamma1.1 and Vgamma2 T cell clonality after intraperitoneal injection of purified protein derivatives (PPD) by the heterogeneity of the third complementarity determining region (CDR3) length in Vgamma1.1-Jgamma4-Cgamma4 and Vgamma2-Jgamma1-Cgamma1 junctions. The V-J junctions were analyzed in intrahepatic lymphocytes (IHL), spleen cells, and peritoneal exudate cells (PEC) by polyacrylamide gel electrophoresis. Gammadelta T cells expressing Vgamma1.1 and Vgamma2 genes were heterogeneous in normal mice. Accumulation of specific Vgamma1.1 T cell clones was transiently detected 7 days after the injection in PEC, but no accumulation was observed in IHL and spleen cells. The accumulated clones disappeared by 4 weeks. Transient accumulation of Vgamma2 T cell clones was also observed in PEC at the early phase after the injection. These results suggest that gammadelta T cells with specific TCR respond to PPD and temporary accumulate in the peritoneal cavity, but not in liver and spleen.

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PubMedDate not supplied

The liver as a potential hematolymphoid organ examined from modifications occurring in the systemic and intrahepatic hematolymphoid system during liver regeneration after partial hepatectomy.

In order to investigate whether or not the adult murine liver can function as one of the hematolymphoid organs, we studied the alteration of cellular characteristics in the systemic and intrahepatic hematolymphoid systems during liver regeneration after partial hepatectomy. Liver regeneration affects the systemic hematolymphoid system, as can been seen from the transient increase in colony forming unit in culture (CFU-C) frequency observed in the bone marrow at 20 hr and its gradual increase in the spleen up to the 6th day after partial hepatectomy. CFU-C were found not only in peripheral blood lymphocyte-rich fraction (PBL), but also in intrahepatic lymphocyte-rich fraction (IHL) of the normal adult liver. CFU-C frequency showed a weak increase in PBL and a dramatic increase, up to the 6th post-hepatectomy day, in IHL subfraction cells, forming a very strong liver association. Colonies, which were generated from IHL in a fibrin clot culture system, were mainly composed of granulocytes, macrophages and mast cells. Wheat germ agglutinin (WGA) positive cells too were detected in IHL and found to increase after partial hepatectomy. IHL of the normal liver were proliferated not only by IL-3 and GM-CSF but also by IL-2. The proliferative responses of IHL to these cytokines were further augmented on day 6 after partial hepatectomy. Similar results were obtained in peripheral blood and splenic lymphocyte-rich fractions. These observations, therefore, suggest that the adult murine liver has hematolymphoid cells as its component and has the function of a hematolymphoid organ closely associated with the systemic hematolymphoid system.

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PubMedDate not supplied

Production of granulocyte-macrophage colony-stimulating factor by adult murine parenchymal liver cells (hepatocytes).

In order to investigate the hematolymphoid system in the adult murine liver, we examined colony-stimulating factor (CSF) released from primary cultured liver cell fractions, parenchymal and nonparenchymal liver cells (more than 99% pure. Using a fibrin clot culture system, we found colony-stimulating activity not only in the culture supernatant from nonparenchymal fraction of normal liver cells (NP-NLC sup), but also in the culture supernatant from parenchymal fraction of normal liver cells (P-NLC sup). Clusters and colonies, which were generated in 4-day cultures of bone marrow cells or spleen cells with P-NLC sup or NP-NLC sup, were mainly composed of granulocytes (G), macrophages (M), and granulocytes and macrophages (GM). Both P-NLC sup and NP-NLC sup proliferated IC2, which is a GM-CSF and IL-3 dependent cell line, and this proliferation was completely inhibited by rabbit anti-murine GM-CSF antibody. Furthermore, both Northern blot analysis and in situ hybridization with specific cDNA probe for murine GM-CSF showed that parenchymal liver cells expressed GM-CSF mRNA transcripts. The present findings indicate that cultured murine parenchymal liver cells produce GM-CSF. The possibility, therefore, is suggested that parenchymal liver cells also play an important role in the regional hematolymphoid system of the liver.

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PubMedDate not supplied

Modification of T-lymphocyte subsets in peripheral blood, the liver, and the spleen during liver regeneration after partial hepatectomy of mice.

Flow cytometry analysis was performed to investigate the modifications to the T lymphocytes in peripheral blood, the spleen, and two intrahepatic lymphocyte fractions--the intrahepatic lymphocyte fraction 1 (IHL Fr.1), which is easily washed out from the liver by perfusion of collagenase solution, and the intrahepatic lymphocyte fraction 2 (IHL Fr.2), which remains in the liver after the perfusion--occurring in the liver regeneration process after partial hepatectomy of mice. The following findings were obtained: 1) The nontreated murine liver contains Thy 1.2+ cells, alpha beta TCR+ cells, gamma delta TCR+ cells, CD4+ cells, and CD8+ cells. 2) The percentage of each T-cell subset in IHL Fr.1 shows an intermediate value between that in the peripheral blood lymphocytes (PBL) and that in the IHL Fr.2. 3) One day after partial hepatectomy, the Thy 1.2+ cells, alpha beta TCR+ whole cells, and CD4+ cells in IHL Fr.2 all showed a transient, yet significant, decrease, but did not reveal any major change in the other fractions. 4) Both the alpha beta TCR dull+ cells and the CD8+ cells showed practically no change after partial hepatectomy in any of the fractions. This indicates that the alpha beta TCR dull+ cell/alpha beta TCR+ whole cell and the CD8+ cell/CD4+ cell ratios show a significant increase 1 day after partial hepatectomy only in the IHL Fr.2. Double-positive cells, which were scarcely found in the spleen of nontreated mice, appeared in the spleen after partial hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

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