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Biomedical subjects

T Noma

Publications and source records attributed to T Noma.

At least 91 records · Page 5Linked to original sources
PubMed1995

Regulation of human IgG subclass production by cytokines: human IgG subclass production enhanced differentially by interleukin-6.

Peripheral blood mononuclear cells (PBMC) stimulated with pokeweed mitogen (PWM) produced increased IgG when cultured with interleukin-6 (IL-6). IgG subclass analysis showed that the presence of IL-6 during the last half of the culture period enhanced IgG1 and IgG4 production. Enhancement of IgG2 synthesis required the presence of IL-6 solely during the last half of the culture period, whereas enhancement paradoxically was blocked by its presence during the first half. The IgG3-enhancing effect of IL-6 was observed only when IL-6 was present throughout the culture period. The critical role of IL-6 was supported by the inhibition of IgG subclass synthesis by anti-IL-6 antibody. PBMC depleted of cells bearing surface IgG of a particular subclass did not synthesize that subclass. This non-responsiveness, which was not reversed even by an addition of IL-6, indicates that the main action of IL-6 is on the differentiation of committed B cells. In addition, IL-6 triggered T cells to produce significant helper activity. These results indicate that IL-6 enhances IgG subclass production differentially and that its critical role in IgG subclass synthesis is in part mediated by T cells, as well as by its direct action on B cells. These findings should be useful for analysing such immune disorders as IgG subclass deficiencies and autoimmune diseases.

Adult↗
PubMed1995

[Interleukin 1 production by peripheral blood mononuclear cells of children with bronchial asthma in remission].

To analyse the change of the immunological response in the remission state of children with bronchial asthma, we studied the interleukin 1 (IL-1) production of peripheral blood mononuclear cells (PBMC) obtained from children with bronchial asthma sensitized by mite antigen. After PBMC were cultured for 24 hours with Dermatophagoides farinae (Df) or lipopolysaccharide (LPS), the PBMC-derived culture supernatant was estimated for IL-1 alpha and beta by enzyme-linked immunosorbent assay (ELISA). PBMC from some of subjects with active asthma produced IL-1 alpha and beta without any stimulation, but not those from controls or subjects in remission. IL-1 alpha and beta production of PBMC stimulated with Df was observed in all three groups, but IL-1 produced by subjects with active asthma was higher than that produced by subjects in the other two groups. Moreover, when PBMC were incubated with LPS, the secretion of both IL-1 alpha and beta was enhanced. PBMC from patients with active asthma produced both IL-1 alpha and beta in amounts comparable to those produced by PBMC from control subjects, but IL-1 production of PBMC from patients in remission was lower than in the other two groups. IL-1 beta production was about ten times as much as IL-1 alpha. Df-induced IL-1 production of PBMC from asthmatic patients sensitized by mite antigen, which was increased in the active state, was down-regulated in the remission state. Moreover, nonspecific stimuli such as LPS may induce the suppressive factors which down-regulate IL-1 production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Regulation of human IgG subclass production by cytokines. IFN-gamma and IL-6 act antagonistically in the induction of human IgG1 but additively in the induction of IgG2.

In this study, we investigated the roles of IFN-gamma and IL-6 in the induction of IgG subclasses from PBMC stimulated with PWM. The presence of IFN-gamma in the first half of the culture period dramatically suppressed the production of IgG1, whereas spontaneous IgG2 secretion was sharply enhanced by IFN-gamma when the latter was present throughout the culture period. Endogenous IFN-gamma was shown to be effective in IgG1 and IgG2 production because IgG1 production was enhanced and IgG2 production was inhibited by the addition of anti-IFN-gamma Ab. Because IFN-gamma did not act on the PBMC depleted of surface IgG2-bearing cells to enhance IgG2, IFN-gamma is unlikely to act as a switching factor. Differing from IFN-gamma, IL-6 enhanced every IgG subclass production as a nonswitching factor, although each of IgG subclasses required IL-6 differentially; maximal IgG1 responses and IgG4 responses occurred when IL-6 was present for the entire culture period or the last half of the culture period, whereas maximal IgG3 responses required the presence of IL-6 for the entire culture period and maximal IgG2 responses were seen when IL-6 was present solely during the last half of the culture period. IFN-gamma antagonized the synthesis of IgG1 by IL-6 and cooperated with IL-6 to produce IgG2. This observation was further supported by the fact that the IL-6-induced IgG1 and IgG2 enhancement were respectively up-regulated and down-regulated by anti-IFN-gamma. Altogether, the critical roles of IFN-gamma and IL-6 were implicated.

Humans↗
PubMed1994

Molecular cloning of a mouse counterpart for human TGF-beta type I receptor.

TGF-beta is a multifunctional polypeptide which is involved in the regulation of cell growth, differentiation, and immunomodulation. Its signaling receptors on the cell surface are postulated to be the type I (TGF beta RI) and type II receptors (TGF beta RII). Previously, TGF beta RII has been cloned and was found to be a receptor type serine/threonine kinase (RSK). In an attempt to isolate novel RSKs expressed in mouse ES cells, we obtained a clone designated as ESK2, which was very closely related to human TGF beta RI. The amino acid sequence of the intracellular domain is completely identical and the transmembrane domain is identical except for one residue. The extracellular domain is 90% homologous with a deletion and an insertion of four amino acid residues. ESK2 also binds to TGF-beta in the presence of TGF beta RII, indicating that ESK2 is the mouse counterpart for human TGF beta RI.

Amino Acid Sequence↗
PubMed1994

Monoclonal proliferation of Epstein-Barr virus-infected T-cells in a patient with virus-associated haemophagocytic syndrome.

Virus-associated haemophagocytic syndrome (VAHS) is a non-neoplastic, generalized histiocytic proliferation disorder showing marked haemophagocytosis associated with systemic viral infection. We describe the case of a 1-year-old girl with Epstein-Barr virus (EBV)-related VAHS, in whom Southern blot analysis showed monoclonal proliferation of bone marrow cells with the EBV genome; detected with the Xho-1 fragment of the latent infection membrane protein genome. EBV serology showed anti-Epstein-Barr virus nuclear associated antigen (EBNA), anti-viral capsid antigen (VCA)-IgG, anti-VCA-IgA elevation and positive EBNA of Sheep red blood cells (SRBC)-rosette-forming bone marrow cells in the late period of her clinical course, indicative of EBV infection. DNA analysis of her bone marrow cells showed monoclonal rearrangement of the T-cell receptor-beta and -gamma chain genes but not of the immunoglobulin heavy chain genes. Those results suggest that EBV may infect T-cells, after which the cells proliferate monoclonally. Repeated administration of epipodophyllotoxin VP-16-213 induced remission, but adrenocortical steroid, vincristine, and cyclophosphamide had no effect on the patient's condition. Ours is a first case report of VAHS showing monoclonal proliferation of EBV-infected T-cells.

Clone Cells↗
PubMed1994

Association of increased numbers of peripheral blood double-negative T-lymphocytes with elevated serum IgG levels in severely handicapped children.

CD3+4-8- double negative cells in peripheral blood lymphocytes were examined in 21 severely handicapped children divided into two groups according to serum IgG level. All children were bedridden and were taking multiple anticonvulsants and there were no apparent clinical differences between these two groups. Serum levels of IgG correlated well with percentages of CD3+4-8- double negative lymphocytes in patients of both groups. In comparisons between the two groups, the high IgG group had higher counts of CD3+4-8- double negative lymphocytes in peripheral blood than the normal IgG group. Two distinct types of double negative cells were identified in the patients with high IgG: one had T-cell antigen receptors of gamma delta heterodimers, the other had receptors of alpha beta chains on their surface. As double negative T-cells are reported to have an important role in defence against bacterial infections, the increased numbers of CD3+4-8- T-cells of both phenotypes in the high IgG patients may reflect exposure to repetitive bacterial stimuli or persistent subclinical infection which in many cases, may be undetectable clinically. Moreover, the hyperimmune states shown by the high serum IgG of these patients may result from the appearance of these unique lymphocytes because they are reported to have a helper function for IgG synthesis in vitro. Taken together, the increased numbers of double negative cells in patients with high IgG may reflect activated defence mechanisms and the development of hyperimmune status.

Adolescent↗
PubMed1994

Effect of interferon-gamma on HLA class 2 expression by antigen-presenting cells inducing Dermatophagoides farinae-specific interleukin-2 responsiveness of lymphocytes in asthmatic children.

As previously reported, antigen-specific IL-2 responsiveness of lymphocytes from patients with bronchial asthma was induced by stimulation with Dermatophagoides farinae, antigen-specifically, in the context of HLA-DQ antigen. We analysed the antigen-presenting processes in the induction of IL-2 responsiveness. Non-adherent responder cells cultured with Df-pulsed autologous adherent cells acquired IL-2 responsiveness, which decreased after prolonged culture of adherent cells for 72 h before recombination with fresh autologous non-adherent cells. HLA-DQ expression on cultured adherent cells also decreased in parallel with the reduction of their ability to induce IL-2 responsiveness. However, the treatment of adherent cells with IFN-gamma restored the expression of these HLA-Class 2 antigens mainly on CD14+ antigen-presenting cells (monocytes), but not on CD20+ cells (B cells), which overcame the decrease of Df-induced IL-2 responsiveness during prolonged culture. These data suggest that IFN-gamma potentiates the up-regulation of Df-specific IL-2 responsiveness, which is likely to depend on the restoration of HLA-DQ expression on monocytes.

Animals↗
PubMed1994

[Suppressive effect of oxatomide on the induction of IL2 responsiveness by DF-stimulated lymphocytes from patients with bronchial asthma].

Oxatomide is an anti-allergic agent having an anti-histamine effect, and has been widely used for clinical purposes. The effect of oxatomide-treatment on the induction of IL2 responsiveness by Df-stimulated lymphocytes was studied in patients with bronchial asthma. Oxatomide alone has almost no effect on lymphocyte activation. Patient's lymphocytes pretreated with 2 to 2000 ng/ml doses of oxatomides for 24 to 48 hours failed to produce Df-induced IL2 responsiveness in a dose-dependent manner. The target cells for oxatomide's suppressive effect were antigen-presenting cells such as macrophages and dendritic cells rather than responder T cells. PPD-induced IL2 responsiveness was also suppressed by the treatment, but the Con A-induced response was not. The results suggest that oxatomide has a slight immunosuppressive capability to block the induction of IL2 responsiveness by Df-stimulated patient's lymphocytes, resulting in the decreased production of such lymphokines as IL2, IL3, IL4, IL5, in a lymphokine cascade of allergic responses, in addition to inhibition of the degranulation and activation of inflammatory cells such as mast cells/basophils and eosinophils.

Animals↗
PubMed1994

Initial events and T cell activation in lymphokine-mediated allergic responses in patients with hen egg allergy.

Specific induction of IL2-responsiveness by ovalbumin-stimulated lymphocytes was studied in patients with hen egg allergy. Fluorescence-activated cell sorter analysis of the cells showed that the IL2-absorbing and IL2-responding cells mainly consisted of CD3+2+4+8-45RA+ cells that may act as helper cells for IgE production and/or as effector cells for delayed type hypersensitivity. beta-Chains (P75) of IL2 receptors were involved in ovalbumin-induced IL2 responsiveness of the patients' lymphocytes, whereas the alpha-chains (p55) were expressed on normal lymphocytes stimulated with ovalbumin as well. Adhering mononuclear cells from patients allergic to ovalbumin but not to Dermatophagoides farinae (Df) were pulsed with ovalbumin antigen then added to a T cell-rich population. After five days of culture, we evaluated cell growth for IL-2 sensitivity during an additional 3-day culture in the presence of IL-2. Responder cells from the patients, which were cocultured with ovalbumin-pulsed autologous adhering cells, acquired IL2 responsiveness; whereas, those cultured with Df-pulsed adhering cells did not. This reaction was specific for antigen. The monoclonal antibody to HLA-DQ (Leu 10) and HLA-DP (HLA-DP) frameworks, but not the one to the HLA-DR framework (OKIa1), blocked the antigen presenting cells ability to induce responses. T Cell-rich responder cells depleted of CD4+ cells did not acquire IL2-responsiveness, whereas the depletion of CD8+ cells had no effect. As a whole, the results indicate that DQ-bearing and/or DP-bearing adhering cells have a key function in presenting ovalbumin-antigen to allergen-specific responder T cells that very likely belong to CD4+ subsets.

Antigen-Presenting Cells↗
PubMed1994

[Spontaneous IgE production in asthmatic children].

In this study, we demonstrated spontaneous IgE production by peripheral blood mononuclear cells of asthmatic children. In 26 asthmatic children, the level of spontaneous IgE ranged 0.1-15.0 IU/ml and in 5 healthy normal children showed under 0.051 IU/ml. In 5 of asthmatic children, specific antibody of Dermatophagoides farinae was detected from PBMC by CAP RAST. In healthy normal children, specific antibody of Df was not detected. Spontaneous IgE production by PBMC and serum IgE level showed well correlation (gamma = 0.835, p < 0.001). Spontaneous IgE production and specific antibody of Df by PBMC also showed well correlation (gamma = 0.717, p < 0.001) IgE production of asthmatic children was inhibited by IFN-gamma.

Adolescent↗
PubMed1994

[Analysis and regulation of interferon-gamma production by peripheral blood lymphocytes from patients with bronchial asthma].

As with normal lymphocytes, small amounts of interferon-gamma (IFN-gamma) were spontaneously produced by lymphocytes from patients with bronchial asthma, and this bronchial asthma, and this production was markedly enhanced by concanavalin A (Con A) stimulation. Distinct from normal lymphocytes, however, IFN-gamma synthesis from patients' lymphocytes decreased in a dose dependent manner on stimulation with Dermatophagoides farinae (Df) antigen. IFN-gamma-producing cells are defined as being of the CD4+ 45RO+ T cell subset, which failed to produce IFN-gamma in Df-stimulated patients' lymphocytes. As the decreased production of IFN-gamma by antigenic stimulation was exclusively induced by Df antigen, but not by ovalbumin (OVA) or Japanese cedar (JC) antigen, it is concluded that Df antigen specifically suppressed IFN-gamma production in patients' lymphocytes. The IFN-gamma synthesis from normal lymphocytes was suppressed by the addition of IL-4 in a dose dependent manner. Moreover, anti-IL-4 antibody dose dependently enhanced IFN-gamma production from Df-stimulated patients' lymphocytes but not from unstimulated lymphocytes. These results indicate that IFN-gamma production by patients' lymphocytes is suppressed by the endogenous IL-4. Reduced IFN-gamma production in patients' lymphocytes on stimulation with Df antigen may lead to the overproduction of IgE in vivo.

Adolescent↗
PubMed1993

Cell action mechanism of tranilast--effect on the expression of HLA-class II antigen.

We tested the effect of Tranilast [N-(3',4'-dimethoxycinnamoyl anthranilic acid)], one of the anti-allergic agents, on the induction of interleukin 2 (IL2) responsiveness of lymphocytes from patients with bronchial asthma or hen-egg allergy following stimulation with Dermatophagoides farinae (Df) or ovalbumin (OVA), respectively. Mononuclear cells pretreated with Tranilast for 12 h failed to respond to IL2 following incubation with Df or OVA. Also Tranilast inhibited purified protein derivative (PPD)-induced IL2 responsiveness of normal lymphocytes but not the Con A-induced IL2 responsiveness of normal or allergen-sensitized lymphocytes. These results suggested that Tranilast has some immunosuppressive effect in that it inhibits antigen-induced IL2 responsiveness. Separation of potential target cells of Tranilast disclosed that antigen-presenting adherent cells were more susceptible to Tranilast than IL2-responding T-cell rich populations. Expression of HLA-DR and -DQ antigens but not DP antigens on macrophages, was significantly suppressed by treatment with Tranilast, although Tranilast scarcely decreased HLA class II antigens expression on B-cells. The suppression was overcome by interferon-gamma, which was known as an inducer for class II antigen expression. Taken together, Tranilast may suppress antigen-induced IL2 responsiveness by inhibiting HLA-DR and HLA-DQ antigens on macrophages.

Adult↗
PubMed1993

Tissue-specific and developmentally regulated expression of the genes encoding adenylate kinase isozymes.

Adenylate kinase (AK) is known to play an important role in homeostasis of adenine nucleotide metabolism. We isolated cDNAs for rat AK isozymes (AK1, AK2, and AK3), determined their mRNAs in rat tissues by Northern blot analysis, and measured the isozyme activities. Tissue-dependent activities of AK1 and AK2 paralleled the contents of mRNAs. Tissues with high AK1 levels showed low AK2 levels and vice versa, suggesting that tissue-specific expressions of the AK1 and AK2 genes are inversely regulated. AK3 mRNA was detected in most tissues examined, suggesting that AK3 gene expression is constitutive. We further examined developmental changes in mRNAs and enzyme activities of AK isozymes in rat skeletal muscle and liver. In the skeletal muscle, AK1 and AK3 activities started to increase at around the weaning period. AK1 mRNA accumulated at the prenatal stage and further increased during development, while AK3 mRNA was at high levels during the fetal stage and remained fairly constant during development. In the liver, AK2 and AK3 activities started to increase after birth and were further elevated during growth, whereas their mRNAs were present at relatively high levels throughout development. The physiological meanings of the tissue-specific expression of the AK isozyme genes are discussed.

Adenylate Kinase↗
PubMed1993

[Immunological aspects of asthmatic children in remission].

Allergen-activated T cells secrete several kinds of bioactive lymphokines such as IL2, IL3, IL4, IL5 and IFN-gamma. They function as helpers in IgE production involved in immediate type hypersensitivity and/or effector cells in delayed type hypersensitivity in allergic patients. The acquisition of interleukin 2 (IL2) responsiveness by specific antigen-stimulated cells is generally an essential event for the induction of specific immunological phenomena. To investigate the immunological changes in asthmatic children in remission, the induction of IL2-responsiveness and production by Df (Dermatophagoides farinae)-stimulated patient lymphocytes, and Df-induced IFN-gamma production by patient lymphocytes were evaluated. The patients were divided into 3 groups. The remission group (I) consisted of those patients who had had no or only a few asthmatic attacks for more than 2 years without medication. The group of active asthma were divided into 2 groups according to attack frequency and severity (II, partial remission; III, active asthma). IL2 responsiveness and production by Df-stimulated lymphocytes from group II and III were increased. As symptoms improved, the extent of the response subsided to a level comparable to that of normal individuals (group III). IFN-gamma production by Df-stimulated lymphocytes from patients with active asthma was lower than that of normal lymphocytes. In contrast, lymphocytes from patients in complete remission group (I) induced far greater IFN-gamma generation than those from normal and group II and III patients in a Df antigen-dependent manner, which might downregulate Df-induced hyperreactivity for Df-mediated allergic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Analysis of immunosuppressive activity of lecithin-bound iodine (LBI) on antigen-induced IL2 responsiveness in peripheral blood lymphocytes from patients with allergic diseases].

The effect of lecithin-bound iodine (LBI) on antigen-induced IL2 responsiveness, useful in in vitro test for the detection of etiological antigen and disease activity in allergic diseases, was investigated. In peripheral blood mononuclear cells (PBMC) from asthmatic children, LBI suppressed Dermatophagoides farinae (Df)-induced IL2 responsiveness in a dose dependent manner, in a range of 0.01 to 100 micrograms/ml. Similarly, LBI also suppressed ovalbumin (OVA)-induced IL2 responsiveness in PBMC from patients with atopic dermatitis, sensitized with OVA, in concentration of 0.1 to 100 micrograms/ml. Moreover, purified protein derivative (PPD)-induced IL2 responsiveness was equally inhibited by LBI, at doses of between 0.1 and 100 micrograms/ml. However, LBI could not overcome the responses induced by concanavalin A (Con A) until it reached unphysiological concentrations of as high as 100 micrograms/ml. The fact that antigen-induced IL2 responsiveness was suppressed by LBI at concentrations comparable to blood levels of LBI in individuals medicated suggests that LBI is a weak immunosuppressant. IL2-responding T cells were more sensitive to LBI than antigen-presenting cells in Df-induced IL2 responsiveness, although LBI suppressed both cell populations. Taken together, LBI could work as a weak immunosuppressant to inhibit lymphocyte responses to allergen and to improve clinical status in allergic diseases, including bronchial asthma caused by Df and atopic dermatitis provoked by OVA.

Antigens↗
PubMed1993

[Skin reaction(s) to culture supernatant(s) from Dermatophagoides farinae (Df)-stimulated lymphocytes, and their correlation with Df-induced interleukin 2 responsiveness by lymphocytes from patients with bronchial asthma].

To investigate the inflammatory function of Dermatophagoides farinae (Df)-activated lymphocytes, supernatants from cultures of the lymphocytes were intracutaneously injected into donors' forearms. Injection of the supernatants of Df-stimulated lymphocytes from mite-sensitized atopic individuals with such diseases as bronchial asthma induced a profound inflammatory reaction in the autologous skin, characterized by erythema extending more than 15 mm in mean diameter and edema. The inflammation was at its peak after approximately 20 min, which was followed by gradually re-growing erythema lasting for as long as 24 hours after injection. Supernatants of unstimulated lymphocytes were also capable of inducing the same reaction, indicating the presence of in vivo activated lymphocytes, although the extent of the response was always smaller. The induced response in normal individuals was erythema of less than 15 mm in mean diameter. The supernatants obtained from cultures at 4 degrees C failed to induce such inflammation. The culture supernatants of ovalbumin-restimulated lymphocytes were also incapable of augmenting the response. The combined data show that the production of inflammatory response-inducing factor(s) from Df-stimulated lymphocytes was antigen specific. Significant skin reactions was correlated with the IL2 responsiveness of Df-stimulated lymphocytes. The skin reaction induced by factor(s) derived from Df-stimulated lymphocytes, which might be similar to the bronchial hyperreactivity of patients with bronchial asthma. The in vitro assay for Df-induced IL2 responsiveness by lymphocytes might reflect the in vitro immediate, late and/or delayed type hypersensitivity.

Animals↗