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Biomedical subjects

K Nomoto

Publications and source records attributed to K Nomoto.

At least 325 records · Page 18Linked to original sources
PubMed1994

Analysis of the role of natural killer cells in Listeria monocytogenes infection: relation between natural killer cells and T-cell receptor gamma delta T cells in the host defence mechanism at the early stage of infection.

We have reported that T cells bearing T-cell receptors (TcR) of gamma delta type (gamma delta T cells) appear in the peritoneal cavity in a relatively early stage of primary intraperitoneal (i.p.) Listeria monocytogenes infection, and play a significant role against the infection. To elucidate the protective role of natural killer cells which also appear in the early stage of L. monocytogenes infection, mice were treated with anti-NK1.1 monoclonal antibody (mAb) to deplete NK cells before the infection. They exhibited accelerated clearance of L. monocytogenes, accompanied by enhanced induction of gamma delta T cells in the peritoneal cavity compared with non-treated mice. When the mice were depleted of gamma delta T cells by in vivo administration of anti-TcR gamma delta mAb, the bacterial burdens of organs from infected mice were not affected by NK cell depletion. These results suggest that, although NK cells increase significantly during the early stage of L. monocytogenes infection, they do not take part in the early host resistance against i.p. L. monocytogenes infection. It is also suggested that increased gamma delta T cells in the peritoneal cavity of NK cell-depleted mice can be one of the factors responsible for the enhanced clearance of L. monocytogenes in the early stage of infection.

Animals↗
PubMed1994

Inhibition of allograft rejection by anti-T-cell receptor-alpha beta monoclonal antibodies preserving resistance to bacterial infection.

Anti-CD3 monoclonal antibody (mAb) has been administered in clinical organ transplantation to reverse acute allograft rejection; however, severe immunodeficiency can result from such mAb treatment and cause an increased incidence of opportunistic infections. Therefore, new model systems are required in order to establish better methods for suppressing allograft rejection while preserving resistance to opportunistic infections. In this study, we compared the effects of the in vivo administration of anti-T-cell receptor-alpha beta (TcR alpha beta) mAb, H57-597, with those of anti-CD3 mAb, 145-2C11. Much to our surprise, the in vivo administration of anti-TcR alpha beta mAb prior to skin grafting led to a longer allograft survival than that of anti-CD3 mAb at any of the comparable dosages examined. In the lymphoid organs of mice treated with anti-TcR alpha beta mAb, TcR alpha beta-bearing cells were almost completely depleted, while TcR gamma delta-bearing cells remained at a relatively increased level on day 14 after anti-TcR alpha beta mAb treatment. The in vitro stimulation by anti-TcR gamma delta mAb clearly showed that such TcR gamma delta-bearing cells were functionally intact. Furthermore, the mice treated with anti-TcR alpha beta mAb, but not anti-CD3 mAb, were observed to be resistant to infection with Listeria monocytogenes. Finally, treatment with H57-597, but not with 145-2C11, led to a marked prolongation of skin allograft survival in the thymectomized mice. These results strongly suggest that anti-TcR alpha beta mAb, which partially preserved anti-bacterial resistance, may be more effective in preventing graft rejection than anti-CD3 mAb in the periphery, and indicate that anti-TcR alpha beta mAb may thus be potentially applicable for human transplantation. In addition, these results also indicate that the TcR gamma delta-bearing cells alone, at least in the absence of TcR alpha beta-bearing cells, do not contribute to allograft rejection in vivo.

Animals↗
PubMed1994

Accumulation enhancement of human monoclonal antibody HB4C5 to lung tumor xenografts by N-deglycosylation.

UNLABELLED: The fractional uptake of intact monoclonal antibodies by tumors is relatively low. Various methods to alter the molecular structure have been used to augment tumor uptake. These chemical manipulations, however, may alter the specificity of antibody binding. METHODS: Comparative studies of biodistribution, radioimmunoimaging and macroautoradiography in LC-6 xenografted mice were conducted with the 125I-labeled intact and N-terminal deglycosylated monoclonal antibodies to evaluate the effect on deglycosylation on antibody binding. RESULTS: The removal of N-glycosyl residues from this monoclonal antibody significantly enhanced specific localization of the radioactivity to the tumor, especially to its necrotic fraction. Nonspecific accumulation of radioactivity to the necrotic fraction of the tumor was excluded by biodistribution studies demonstrating selective accumulation of 125I-labeled monoclonal antibody after coadministration of 125I-monoclonal antibody (intact or N-deglycosylated) with 131I-labeled control IgM. CONCLUSION: The lung cancer-associated human monoclonal antibody HB4C5, which recognizes histone H2B as the antigen, accumulates specifically to the necrotic fraction of tumor. The uptake is enhanced by removal of N-terminal glycosyl residues from the antigen-binding site of the light chain.

Animals↗
PubMed1993

Characterization of lung squamous cell carcinoma-derived T-cell suppressive factor.

BACKGROUND: The immunosuppressive state of a tumor-bearing patient is possibly mediated by tumor-derived factor. In this study, the authors characterized lung squamous cell carcinoma-derived immunosuppressive factor (LSCF). METHODS: The immunosuppressive activity of QG56 (a lung squamous carcinoma cell line)-derived LSCF was evaluated by the effect of culture supernatant of QG56 on anti-CD3 monoclonal antibody-induced T-cell, response such as proliferation (3H-thymidine uptake), cytotoxicity (51Cr-releasing assay), and expression of cytokine mRNA (polymerase chain reaction). The LSCF was partially purified with an ion-exchange high-performance liquid chromatography (HPLC) and a gel-filtration HPLC. RESULTS: The LSCF inhibited proliferation, cytotoxicity, and expression of cytokine mRNA of T-cells in a dose-dependent manner. It has a molecular weight of approximately 22 kd, and was sensitive to proteinase K, heating at 60 degrees C, and resistant to treatment with trypsin and pH 3 and 9. These properties appear to be similar to those of transforming growth factor-beta (TGF-beta). However, the activity of the LSCF was not abrogated by anti-TGF-beta sera, and the LSCF did not suppress the proliferation of TGF-beta-sensitive mink lung cells (Mv1Lu). CONCLUSIONS: These data suggest that LSCF may be a novel tumor-derived immunosuppressive protein factor.

Base Sequence↗
PubMed1993

Appearance of TCR-alpha beta+ CD4-CD8- skin intraepithelial lymphocytes in radiation bone marrow chimeras.

Thymocytes expressing homogeneous TCR V gamma 5/V delta 1 gene without N nucleotide addition (canonical sequence) have been reported to be positively selected in fetal thymus. Because skin intraepithelial lymphocytes (s-IEL) also express canonical sequence, it is proposed that s-IEL are generated by an epidermis-specific homing of these positive selected fetal V gamma 5/V delta 1-bearing thymocytes. We have reported that positive selection of V gamma 5+ thymocytes is not seen in AKR/J-->C3H/He bone marrow chimeras. In this report, we analyzed the phenotype of donor-derived s-IEL from AKR/J-->C3H/He bone marrow chimeras that appeared in the absence of positive selection of V gamma 5-bearing thymocytes. We found interestingly that almost all donor-derived s-IEL in the bone marrow chimeras expressed TCR-alpha beta lack expression of both CD4 and CD8. Furthermore, TCR-alpha beta+ s-IEL were detected in adult-thymectomized bone marrow chimeras, indicating that the TCR-alpha beta+ s-IEL are extrathymically derived. All these results suggest that the s-IEL expressing TCR-alpha beta appear extrathymically in the absence of positive selection of V gamma 5/V delta 1-bearing thymocytes. Our results may also explain the contradicting result between human s-IEL, which are TCR-alpha beta+ CD4- CD8- and murine s-IEL, and suggest the importance of extrathymic T cell differentiation pathway of the TCR-alpha beta lineage in immune surveillance.

Animals↗
PubMed1993

Peritoneal gamma delta T cells induced by Escherichia coli infection in mice. Correlation between Thy-1 phenotype and host minor lymphocyte-stimulating phenotype.

We found that gamma delta T cells increased in number in the peritoneal cavity after i.p. inoculation with Escherichia coli (ATCC 26) in mice. The increase of the gamma delta T cells was most prominent on day 5 after inoculation when the pathogens had been already eliminated from the hosts. Two-color flow cytometric (FCM) analysis revealed that these gamma delta T cells in infected C57BL/6 mice expressed Thy-1 Ag on their cell surface. On the other hand, gamma delta T cells induced by E. coli inoculation in C3H/He mice contained Thy-1-negative gamma delta T cells in addition to the Thy-1-positive gamma delta T cells. In both strains, irrespective of Thy-1 Ag expression, these gamma delta T cells were CD5 negative, CD44 positive, L-selectin negative, Ly-6C negative, and IL-2R low positive. Analyses of peritoneal exudate cells (PEC) from several other strains of mice after E. coli inoculation suggested that Thy-1-negative gamma delta T cells appear in mice carrying endogenous superantigen specific for V beta 3, especially mammary tumor virus-6. These findings suggest that Thy-1 Ag expression on the gamma delta T cells appearing in the peritoneal cavity after i.p. E. coli inoculation is correlated to the Mls phenotype of the host mice.

Animals↗
PubMed1993

Extensive apoptosis occurring in the thymus during accelerated rejection of cardiac allografts in presensitized rats.

Cardiac allografts of (Lewis x Brown Norway) F1 rats are rejected by Lewis recipients at 7.5 days after engrafting. When recipients are presensitized with Brown Norway skin grafts at 7 days before engrafting, the cardiac grafts are rejected between 24 and 36 h (accelerated rejection, ACR). We previously demonstrated that the number of thymocytes in recipients showing ACR is decreased to approximately one eighth at 24 h after engrafting, and the thymocytes remaining in the thymus are phenotypically and functionally more mature. In the present study, flow cytometric analysis of the thymocytes in the sensitized recipient at 24 h after engraftment demonstrated that the frequency of single positive cells (CD4+CD8- and CD4-CD8+) was increased and that of double positive cells (CD4+CD8+) was decreased, indicating that immature thymocytes preferentially disappeared during the ACR episode. Thymocytes of the recipients undergoing ACR suffered from extensive apoptosis, characterized by chromatin condensation in the nuclei, cell shrinkage, nuclear collapse, and DNA fragmentation. Serum levels of corticosterone were elevated but were within a similar range among the transplant recipients destined for acute rejection, those undergoing ACR, and isografted controls, suggesting the participation of mediator(s) other than glucocorticoid in the induction of extensive apoptosis in the transplant recipients with ACR. We propose that thymocyte apoptosis is accelerated during the allograft rejection episode.

Animals↗
PubMed1993

WWamide-1, -2 and -3: novel neuromodulatory peptides isolated from ganglia of the African giant snail, Achatina fulica.

Three novel neuropeptides, isolated from ganglia of the African giant snail, Achatina fulica, were named WWamide-1, -2 and -3. These substances were biologically active heptapeptide amides with a Trp residue at both the N- and C-termini. WWamide-1, which displayed an inhibitory activity on a central neuron of the snail, exhibited peripherally modulatory effects on muscular contractions of not only the gut and other tissues of the snail but also certain tissues of other molluscs.

Amino Acid Sequence↗
PubMed1993

Two novel tachykinin-related neuropeptides in the echiuroid worm, Urechis unicinctus.

Two novel neuropeptides, urechistachykinin I (H-Leu-Arg-Gln-Ser-Gln-Phe-Val-Gly-Ser-Arg-NH2) and urechistachykinin II (H-Ala-Ala-Gly-Met-Gly-Phe-Phe-Gly-Ala-Arg-NH2), were isolated from the ventral nerve cords of the echiuroid worm, Urechis unicinctus. These peptides showed a contractile action on the inner circular body-wall muscle of the animal. Their amino acid sequences were found to be significantly homologous with those of the vertebrate and insect tachykinins. The urechistachykinins potentiated spontaneous rhythmic contractions of the cockroach hindgut.

Amino Acid Sequence↗
PubMed1993

Two-dimensional echocardiographic assessment of papillary muscle contractility in patients with prior myocardial infarction.

OBJECTIVES: This study was performed to assess the length and contractile performance of human left ventricular papillary muscles and to determine the relation between papillary muscle dysfunction and mitral regurgitation. BACKGROUND: Assessment of human papillary muscle contractility remains a clinical challenge. METHODS: Two-dimensional echocardiographic examinations were performed in 16 normal subjects and 31 patients with prior myocardial infarction. Apical echocardiograms were used to obtain long-axis views of the anterior and posterior papillary muscles. The end-systolic and end-diastolic lengths of the papillary muscles were measured and fractional shortening was calculated. RESULTS: Fractional shortening in normal subjects was 27 +/- 8% for the anterior papillary muscle and 30 +/- 8% for the posterior papillary muscle. In patients with prior myocardial infarction, a significant decrease in fractional shortening was observed in proportion to the severity of left ventricular wall motion abnormalities at the site of papillary muscle implantation. Moderate or severe mitral regurgitation was significantly more frequent in patients with combined anterior and posterior papillary muscle dysfunction than in those with isolated anterior or posterior dysfunction or with normal function of both papillary muscles (p < 0.05). CONCLUSIONS: Two-dimensional echocardiography is useful for demonstrating abnormal contractility of human left ventricular papillary muscles. Papillary muscle contractility should be analyzed in each case to elucidate the mechanism of mitral regurgitation in patients with papillary muscle dysfunction.

Adult↗
PubMed1993

Role of peripheral hemopoietic chimerism in achieving donor-specific tolerance in adult mice.

The role of peripheral hemopoietic chimerism in the induction and maintenance of donor-specific tolerance was investigated by our tolerance-inducing method using cyclophosphamide (CP). As has been previously reported, CP injection at a dose of 200 mg/kg to C3H (Thy-1.2, Mls-1b) mice 2 days after priming with 10(8) viable AKR (Thy-1.1, Mls-1a) spleen cells (SC) resulted in both establishment of mixed chimerism and selective elimination of V beta 6+CD4+ T cells in the periphery. When, instead of viable SC, 1300 rad irradiated 10(8) AKR SC were used for priming to C3H mice, CP treatment 2 days after the priming also caused significant but, as compared with priming with nonirradiated viable cells, incomplete elimination of V beta 6+ T cells in the periphery. In these mice, no hemopoietic chimerism was found. In parallel with this incomplete elimination of peripheral V beta 6+ T cells, LN cells of these mice showed reduced but considerable response to AKR SC. However, once hemopoietic chimerism was introduced to these incompletely tolerant mice by an injection with donor-type viable [AKR x C3H]F1 SC 2 days after CP-treatment, LN cells from these newly established chimeras, irrespective of presence or absence of the thymus, became completely nonresponsive to AKR while preserving normal response to BALB/c (third party). This state of nonresponsiveness was accompanied by clonal elimination of the remaining V beta 6+ T cells in the periphery. These results indicate that peripheral chimerism promoted profound tolerance to donor-Mls Ag specifically. Furthermore, from experiments of skin grafting, we demonstrated that tolerance to minor histocompatibility Ag was also achieved in the presence of peripheral hemopoietic chimerism.

Animals↗
PubMed1993

A simple quantitative in vitro assay for thymocyte adhesion to thymic epithelial cells using a fluorescein diacetate.

Recent data verified the role of thymocyte adhesion to thymic epithelial cells (TEC) in T cell development. In order to measure this cellular event as one of routine examinations in immunological studies, a simple quantitative assay in in vitro setting is required. Labeling thymocytes with fluorescein diacetate (FDA) was used to measure quickly and with certainty the adhesion ability of BALB/c thymocytes to TEC cells, a thymic epithelial cell line derived from BALB/c mouse thymic stroma. Thymocytes stained with FDA at the concentration of 2.5 micrograms/ml gave a strong fluorescent intensity (FI) easily detectable in a spectrophotometer and showed the same phenotypical and functional features as unstained cells. As it was confirmed that the cell number correlated well with FI, the number of cells adhering to TEC in wells of a 96-well microplate could be estimated. The major advantage of using FDA was that it took only a few seconds to measure FI of one sample. In contrast, to count the number of adherent cells with conventional methods using a light microscope or radioisotopes required much longer time and care to avoid radiological hazards. Moreover, cell viability and FI of FDA-labeled thymocytes changed little for 24 h, and lysates of FDA-positive cells demonstrated the same FI as living cells. These results indicate that many samples could be applied for FI measurement at the same time after in vivo or in vitro experiments.

Animals↗
PubMed1993

Autoreactive and heat shock protein 60-recognizing CD4+ T-cells show antitumor activity against syngeneic fibrosarcoma.

A CD4+ heat shock protein (hsp) 60-recognizing autoreactive T-cell line (BASL1) and clone (BASL1.1) were examined for their antitumor activity against major histocompatibility complex class II- syngeneic Meth A fibrosarcoma (Meth A), which was immunofluorescently stained with monoclonal antibody specific for hsp 60. In in vitro proliferative assay, BASL1.1 was suggested to recognize Meth A-derived hsp 60 presented by syngeneic antigen-presenting cells in a major histocompatibility complex class II-restricted manner. This cell line and clone showed antitumor activity in tumor-neutralizing (Winn) assay. BASL1 and BASL1.1 cells produced gamma-interferon, tumor necrosis factor, and interleukin 2 but not interleukin 4 by the stimulation with syngeneic spleen cells. In cytolytic assay, these cell lines and clones showed neither direct nor indirect (bystander) cytolysis against Meth A. In cytostatic assay, these cells inhibited the proliferation of Meth A in the presence of syngeneic macrophages, and this activity was abrogated by the addition of anti-gamma-interferon monoclonal antibody. Recombinant gamma-interferon could induce cytostatic activity only in the presence of macrophages, and tumor necrosis factor synergized this activity. Antitumor activity induced by BASL1 was abrogated by the administration of anti-CD8 monoclonal antibody in vivo, suggesting that CD8+ cytotoxic T-lymphocytes are essential and final effector cells for BASL1-mediated Meth A rejection. These findings indicate that CD4+ autoreactive and hsp 60-recognizing T-cells show two types of antitumor activity: cytostasis and induction of tumor-specific cytotoxic T-lymphocytes. Furthermore, these results imply that tumor-specific immunity could be elicited by CD4+ helper T-cells which recognize hsp.

Animals↗
PubMed1993

Early appearance and activation of natural killer cells in tumor-infiltrating lymphoid cells during tumor development.

We investigated NK cell infiltration into tumor developing lesions at early stage of tumor development after intraperitoneal inoculation of 3LL lung carcinoma into syngeneic C57BL/6 mice. Natural killer (NK) cells, which were detected by anti-NK 1.1 monoclonal antibody (mAb), remarkably increased in number in tumor-developing lesions (peritoneal cavity) as early as day 3 after inoculation of 3LL. The tumor-infiltrating NK cells from 3LL-inoculated mice produced a high level of interferon-gamma by co-culture with 3LL and showed enhanced cytotoxic activities against both NK-sensitive (YAC-1) and NK-resistant (3LL and P815) tumors. Furthermore, mice depleted of NK cells by injection of anti-NK 1.1 mAb or anti-asialo GM1 antibody showed shorter survival times after intraperitoneal inoculation of 3LL when compared with control mice. These results suggest that NK cells infiltrate the tumor-developing lesion at an early stage and may participate in the early protection against tumors through production of a high amount of interferon-gamma and enhanced cytotoxicity at tumor-bearing sites.

Animals↗
PubMed1993

Thymus-derived cytokine(s) including interleukin-7 induce increase of T cell receptor alpha/beta+ CD4-CD8- T cells which are extrathymically differentiated in athymic nude mice.

Extrathymic T cell differentiation pathways have been reported, although the thymus is the main site of T cell differentiation. The thymus is also known to produce several cytokines that induce proliferation of thymocytes. In the present study, we investigated the influence of thymus-derived cytokines on extrathymic T cell differentiation by intraperitoneal implantation with a diffusion chamber which encloses fetal thymus (we named it fetal thymus-enclosed diffusion chamber, FTEDC) in athymic BALB/c nu/nu mice. Increase in number of T cells bearing T cell receptor (TcR) alpha/beta was detected in lymph nodes and spleens of FTEDC-implanted nude mice 1 week after implantation, whereas no such increase was detected in control nude mice implanted with a diffusion chamber without thymus. The FTEDC-induced increase of T cells was suppressed by intraperitoneal injection of anti-interleukin-7 monoclonal antibody (mAb). The TcR alpha/beta T cells in FTEDC-implanted BALB/c nu/nu mice preferentially expressed V beta 11, although V beta 11-positive T cells are deleted in the thymus of euthymic BALB/c mice by clonal elimination of self-super-antigen Dvb11-specific T cells. TcR alpha/beta T cells in FTEDC-implanted nude mice were of CD4-CD8- phenotype and showed no proliferative response against anti-TcR monoclonal antibody stimulation. These results suggest that the thymus can induce extrathymic T cell differentiation through the influence of thymus-derived cytokine(s) including interleukin-7, and that such extrathymically differentiated T cells have acquired only a little or no ability for proliferation when they recognize antigen by their TcR.

Animals↗
PubMed1993

Thymus influences the development of extrathymically derived intestinal intraepithelial lymphocytes.

Overwhelming evidence suggests that the majority of murine small intestinal intraepithelial lymphocytes (IEL) are extrathymically derived. These IEL include those with T cell receptor (TCR) gamma delta and some TCR alpha beta (CD8 alpha alpha and Thy-1-). In contrast, congenitally athymic nude mice have low numbers of gamma delta TCR IEL as well as very few alpha beta TCR IEL, far less than that would be expected if one assumes that gamma delta TCR IEL and alpha beta TCR (CD8 alpha alpha and Thy-1-) IEL in euthymic mice are extrathymically derived. To examine this discrepancy, we followed extrathymic IEL differentiation in IEL of day 3-thymectomized (NTX) mice as another athymic mouse model and found that gamma delta TCR IEL and extrathymically derived alpha beta TCR IEL in NTX mice are markedly reduced, almost to the level of nude mice. We further show that it is probably the absence of a thymic stroma that is responsible for the lower amounts of extrathymically derived IEL in nude mice, as the low amounts can be corrected to euthymic levels by syngeneic fetal thymus grafting but not by direct injection of F1 thymocytes. Lastly, unlike TCR/CD3+ extrathymically derived IEL, we noted a large proportion of extrathymic CD3-CD8- and CD3-CD8+ IEL; they were threefold more frequent in nude and NTX than in euthymic mice. This suggests that the thymus influences extrathymically derived IEL in its development from CD3- to CD3+ at the small intestinal epithelium.

Animals↗