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T Noma

Publications and source records attributed to T Noma.

At least 109 records · Page 6Linked to original sources
PubMed1992

CD4+ CD45RA+ T cells modulate allergen-induced interleukin 2 responsiveness in human lymphocytes.

Peripheral blood lymphocytes from nonallergic individuals acquired responsiveness to interleukin 2 (IL2) after stimulation with ovalbumin (OVA) or Dermatophagoides farinae (Df) antigens when they were pretreated with the CD45RA antibody, which has been shown to define the suppressor inducer subset of CD4+ cells and also to block its suppressor activity. The effect provided by the CD45RA antibody was lost if the lymphocytes had initially been activated with the OVA of Df antigens. The magnitude of the responses was comparable to the allergen-induced responses observed in OVA- or Df-sensitized lymphocytes from allergic patients. The pre-existing IL2 responsiveness in the patients was not increased by the CD45RA antibody pretreatment. However, the CD45RA antibody pretreatment gave rise to Df-induced IL2 responsiveness in the lymphocytes of the patients sensitized with OVA but not with Df; conversely, OVA-induced IL2 responsiveness was enhanced in Df- but not in OVA-sensitized lymphocytes. The CD45RA antibody apparently acts on CD4+ T cells, but not on CD8+ T cells, to induce the IL2 response. A further dissection of normal CD4+ T cells indicated that CD4+45RA- T cells preferentially respond to IL2 after stimulation with OVA or Df antigens. Since normal CD4+45RA+ T cells did not show antigen-induced IL2 responsiveness even after pretreatment with the CD45RA antibody, it is unlikely that the CD45RA antibody stimulates CD4+45RA+ T cells to become responsive to IL2 after antigenic challenge. Alternatively, CD4+45RA+ T cells may modulate the activity of CD4+45RA- T cells, which are potentially responsive to IL2 by antigenic stimulation and thus provide tolerance in nonallergic lymphocytes. Collectively, a defective suppressor activity of CD4+45RA+ T cells may exist in patients with hen-egg allergy and/or bronchial asthma, which may cause lymphocytes to be hyperreactive to OVA or Df antigens.

Adult↗
PubMed1992

[A study of Epstein-Barr virus-associated hemophagocytic syndrome successfully treated with VP16 and analysis of T cell receptor chain genes of the bone marrow cells].

Virus-associated hemophagocytic syndrome (VAHS) is a nonneoplastic, generalized histiocytic proliferation disorder with marked hemophagocytosis associated with a systemic viral infection. We describe a female child with EBV-related VAHS, in whom Southern blot analysis showed monoclonal proliferation of bone marrow cells having EBV genome as detected with Xho-1 fragment of latent infection membrane protein (LMP) genome. The EBV serology showed anti-EBNA, anti-VCA-IgG, anti-VCA-IgA elevation and positive EBNA of SRBC-rosette forming bone marrow cells in late period of her clinical course, which indicated primary infection or secondary alteration of EBV immunity. The DNA analysis of the bone marrow cells also demonstrated monoclonal rearrangement of T cell receptor-beta and -gamma chain genes. Thus our study suggests that EBV might infect T cells and the T cells might proliferate monoclonally. Repeated administration of VP16 was capable of inducing remission of the disease, although adrenocortical steroid, vincristine and cyclophosphamide were administrated unsuccessfully. This is the first case of VAHS in which the monoclonal proliferation of EBV-infected T cells was demonstrated.

Bone Marrow↗
PubMed1992

[Function, molecular structure and gene expression of IL-4].

Interleukin-4 (IL-4) is a T-lymphocyte-derived 20-kDa glycoprotein that has a broad spectrum of biological activity including growth and differentiation of T cells, B cells, mast cells, hematopoietic cells and non-hematopoietic cells. The biological effects of IL-4 are induced by binding to specific membrane receptors (IL-4R) on target cells. Molecular cloning of IL-4R revealed a novel cytokine receptor family, but not clues as to the signalling mechanism. The biochemical mechanism of IL-4 signal, induced by its specific binding, remains to be clarified. Recent studies on the physiological function of IL-4 are presented here.

Amino Acid Sequence↗
PubMed1992

[A rapid measuring technique for allergen-induced IL2 responsiveness of lymphocytes by the propidium iodide-staining method. Detection of the etiological antigen in patients with allergic diseases].

A method for rapidly measuring the interleukin 2 (IL-2)-responsiveness of allergen-stimulated lymphocytes has been newly developed using propidium iodide (PI) staining and drawing ink quenching of the fluid medium fluorescence. There was a linear correlation between the number of PI-stained cells and the fluorescence intensity. The background was less than 5 percent. This fluorochromasia assay reflected the cell number for the quantitative measurement of lymphocyte proliferation. Antigen-activated patient cells added to IL2, showed greater increase in 3H-TdR uptake than IL-2-untreated cells, and were capable of acquiring IL2 responsiveness. Increased numbers of the cells were observed by both the PI- and trypan blue-staining methods. In contrast, unstimulated cells also showed increased 3H-TdR uptake response without increased cell numbers on stimulation with r-IL2 by a 6.8 to 19.3 fold stimulation index compared to the antigen-activated cells. The results indicated that the unstimulated cells in addition with r-IL2 still remained in the initial phase of the DNA-synthetic (S) period through the cell cycle, whereas the activated cells had passed through the post-synthetic gap (C2) and/or cell division at mitosis (M). 3H-TdR uptake of cultured cells usually demonstrates the presence of antigen-sensitized lymphocytes by in vitro proliferative response, and shows an increased stimulation index in 4 or 7 day cultured cells on stimulation with allergens. However, proliferation of some cell populations decreased; furthermore no distinct differences in cell proliferation between allergic and normal lymphocytes were observed, as is usual in this assay, although the present method was capable of measuring increased-IL2 responsiveness of patient lymphocytes. The results indicate that the 3H-TdR uptake method can not be substituted for cell enumeration in the evaluation of the antigen-specificity of induced-IL2 responsiveness of activated cells. Therefore, cell enumeration using the PI-staining method may be preferable in this system. The induced response was observed in lymphocytes from patients with atopic dermatitis, bronchial asthma and/or allergic rhinitis specifically on stimulation with the antigen causing clinical symptoms. The results obtained using the PI-staining method were very similar to those in previous reports where the trypan blue staining method was employed. The present method appears to be capable of rapidly screening etiological antigens for disease and easily monitoring clinical activity.

Allergens↗
PubMed1991

Multiple forms of TGF-beta: distinct promoters and differential expression.

There are now five known distinct isoforms of TGF-beta with 64-82% identity. Of these, only TGF-beta 1, 2 and 3 thus far have been demonstrated to be expressed in mammalian tissues; TGF-beta 4 has been described only in chicken and TGF-beta 5 only in frog. Although the biological activities of these five isoforms of TGF-beta are indistinguishable in most in vitro assays their sites of synthesis and localization in vivo are often distinct. Expression of the various isoforms is differentially controlled both in vivo, as in development, and in vitro after treatment of cells with steroids, such as oestrogen or tamoxifen, or with retinoids. To investigate the basis of these observations we have cloned and characterized the promoters for the human TGF-beta 1, 2 and 3 genes. Significant differences have been found: whereas the TGF-beta 1 promoter has no TATAA box and is regulated principally by AP-1 sites, both the TGF-beta 2 and 3 promoters have TATAA boxes as well as AP-2 sites and cAMP-responsive elements. Accordingly, TGF-beta 1 gene expression is induced strongly by phorbol esters whereas that of TGF-beta 2 and 3 is induced by forskolin, an activator of adenylate cyclase. Expression of TGF-beta 2 and 3 is often coordinately regulated in vivo in a pattern distinct from that of TGF-beta 1.

Animals↗
PubMed1991

Molecular cloning and structure of the human transforming growth factor-beta 2 gene promoter.

Genomic DNA extending over 10 kb 5' of the transforming growth factor-beta 2 (TGF-beta 2) coding region was isolated from a human lung fibroblast lambda phage library. A 5.6 kb Hind III fragment containing the 5'-untranslated region and flanking sequences was subcloned and sequenced. S1 nuclease protection analysis identified a transcriptional initiation site 1357 nucleotides 5' of the methionine initiation codon (ATG). A "TATA box" consensus sequence was identified 30 bp from this transcriptional start site; however, consensus "CAT box" sequences were not observed. Approximately 50 nucleotides of homopurine-pyrimidine [d(GA.CT)50] sequence were identified in the 5'-untranslated region, as well as two short open reading frames of 5 and 45 amino acids. Several AP-1, AP-2, CRE and SP1-like DNA consensus sequence elements were also identified surrounding the transcription initiation site. 5'-deletion mutants of the promoter region were fused to the chloramphenicol acetyl transferase (CAT) gene and promoter activity of the isolated genomic DNA was demonstrated in several cell lines. DNA constructs containing nucleotides between -508 to +63 demonstrated high levels of promoter activity. However, sequences between -778 and -508 nucleotides modulated this promoter activity in a manner which was dependent upon the cell line utilized, suggesting that regulation of TGF-beta 2 gene transcription may be dependent upon the cellular background. The TGF-beta 2 promoter is markedly different from the promoters that have been recently characterized for TGF-beta 1 and TGF-beta 3.

Amino Acid Sequence↗
PubMed1990

Identification of a cord blood T cell subset of CD3+4-8-45R+ suppressing interleukin 2 production in the autologous mixed lymphocyte reaction and the mode of action of exogenous IL2 in the induction of IL2 production.

As previously reported, the inability of cord blood T cells to produce IL2 in the autologous mixed lymphocyte reaction (AMLR) could be recovered by the treatment of stimulator non-T cells with interferon-gamma (IFN-gamma) and of the AMLR with exogenous IL2. In the present study, we showed that addition of untreated autologous cord blood T cells to the above-mentioned AMLR abrogated the IL2 production in a dose-dependent manner, suggesting active suppression by the untreated T cells because untreated cord blood T cells did not consume IL2. Suppressor activity was abrogated by the treatment of cord blood T cells with monoclonal anti-CD3 antibody plus complement or with monoclonal anti-CD45R (Leu 18) antibody, but not by the treatment with monoclonal anti-CD4 antibody and/or anti-CD8 antibody plus complement. These data showed that the cord blood suppressor T cells were CD3+4-8-45R+. This suppressor activity also disappeared by culturing with rIL2 for 8 hr. As the frequency of CD45R+ cord blood T cells was comparable to that of CD45R+ adult T cells and was minimally affected by the IL2 treatment, functional modulation of CD45R+ suppressor T cells by IL2 is suggested. Moreover, in spite of the inhibitory effect of anti-CD45R antibody on the suppressor activity, IL2 production was not induced merely by addition of anti-CD45R antibody directly to the responder cells in AMLR. Taken together, these data suggest the requirement of exogenous IL2 for IL2 production in that IL2-producing-precursor T cells themselves should be stimulated by IL2 in addition to the modulation of CD45R+ suppressor T cells by IL2.

Adult↗
PubMed1990

Effect of ketotifen on antigen-induced interleukin 2 (IL-2) responsiveness in lymphocytes from patients with atopic dermatitis and/or bronchial asthma.

We tested the effect of Ketotifen (4-(1-methyl-4-piperidylidene)-4H- benzo[4,5] cyclohepta[1,2-b]thiophen-10(9H)-one hydrogen (fumarate) on the induction of allergen-induced IL-2 responsiveness in lymphocytes from patients with atopic dermatitis and/or bronchial asthma. Ovalbumin (OVA)- and/or Dermatophagoides farinae(Df)-induced IL-2 responsiveness was increased in almost all patients (1-15 years old) before Ketotifen treatment. Two to 12 months administration of Ketotifen (0.06 mg/kg/day) decreased activity of the response in 7 out of 9 cases corresponding to improvement of clinical symptoms. In in-vitro studies, antigen presenting cells (adherent cells) from the patient pretreated with 5, 50 and 500 ng/ml doses of Ketotifen for 12 h failed to present OVA or Df antigen to T-cells for induction of IL-2 responsiveness. Antigen-pulsed adherent cells also failed to induce the response of the T-cells pretreated with 50 and 500 ng/ml doses of Ketotifen but not with a 5 ng/ml dose. A 50 ng/ml dose of Ketotifen did not affect T-cells for induction of the response. In contrast, the treated adherent cells are capable of presenting PPD antigen or Con A for the induced response. The combined data indicate that induction of IL-2 responsiveness of peripheral blood lymphocytes on stimulation with nominal antigen may reflect an immune response to allergen in patients with allergy and a weak immunosuppressive effect of Ketotifen seems to block the response in the pathogenic process of allergic diseases.

Adolescent↗
PubMed1990

Decreased production and responsiveness of interleukin 2 in lymphocytes of patients with nephrotic syndrome.

Production of and responsiveness to interleukin 2 (IL-2) were evaluated in lymphocytes from 18 patients with nephrotic syndrome. The IL-2 production of T cells, when stimulated with autologous non-T cells separated on a polystyrene resin column, was significantly decreased in patients with minimal-change nephrotic syndrome. No significant difference in the level of IL-2 production was noted between minimal-change nephrotic syndrome patients in the nephrotic stage and those in remission. The IL-2 production was also significantly decreased in lymphocytes from patients with membranous nephropathy. The responsiveness to IL-2 was inconstant among patients with nephrotic syndrome. These results indicate that the immune system of regulating IL-2 production is impaired in patients with nephrotic syndrome.

Adolescent↗
PubMed1990

[Comparative study on maxillo-facial components between human children and Japanese monkeys].

The purpose of this study is to find the cause of the variation of the occlusion and the shape of the maxillo-facial components in the Japanese children at the IIA stage in comparison with the Japanese monkeys. The human materials consist of lateral and P.A. cephalograms of 26 children with a mean age of approximately 4.5 years. The monkey materials consist of dry skulls and their lateral cephalograms. They are categorized into four classes: 18 juveniles, 16 subadults, 17 female adults, and 17 male adults. The factor analysis is employed in this study on 17 measurements which reveal the structure of the maxillo-facial components. The factors of the human children are like those of the Macaca juvenile and female adult. These factors show a tendency that the growth direction of the maxilla is correlated with the cranial base angle and the width of the maxillo-facial components is correlated with its depth. However, as to these factors, human mandibular measurements have a much lower factor loading than those of the Macaca. Contrary to the human, the Macaca's mandibular measurements at every stage and sex are well correlated with the maxillary measurements. These findings suggest that the variation of the human occlusion and the external shape of the maxillo-facial components should be higher than that of the Macaca.

Animals↗
PubMed1990

Ovalbumin-specific induction of IL2 responsiveness in lymphocytes from patients with hen egg allergy and its regulation by the culture supernatant of normal lymphocytes.

Interleukin 2 (IL2) responsiveness of ovalbumin (OVA)-stimulated lymphocytes from patients with hen-egg allergy was studied. The number of viable cells of 5-day cultured lymphocytes stimulated with OVA was increased by an additional three days incubation with recombinant IL2. This phenomenon was not observed when the lymphocytes of patients allergic to OVA but not to Dermatophagoides farinae extract antigen (Df) were stimulated with Df. Normal lymphocytes stimulated with OVA expressed Tac antigen (low affinity IL2 receptor) but, in contrast to those from the allergic patients, did not absorb nor respond to IL2. The induction of OVA-specific IL2 responsiveness in patient lymphocytes was markedly suppressed on the addition of culture supernatant from OVA-stimulated normal T cells, but Df-specific IL2 responsiveness of the lymphocytes from Df-sensitized patients with bronchial asthma was not suppressed by the same supernatant. The supernatant of lymphocytes from allergic patients did not show such suppressive effect. The patient lymphocytes whose IL2 responsiveness was suppressed with the supernatant from normal lymphocytes still expressed Tac antigen. These observations suggest that the culture supernatant of normal T lymphocytes stimulated with OVA contained an antigen-specific factor suppressing the induction of IL2 responsiveness of OVA-stimulated patient lymphocytes. The production of such a suppressive factor was impaired in the patient, and further, the factor may have inhibited the triggering signal of IL2 receptors having absorbed IL2. The existence of some allogeneic barrier between the factor(s) and patient lymphocytes was suggested, since the supernatant from OVA-stimulated normal T cells did not necessarily suppress the response of all patients tested.

Absorption↗
PubMed1990

[Suppressive effect of Saibokuto on Dermatophagoides farinae (Df) antigen-induced IL2 responsiveness of lymphocytes from asthmatic children].

The effect of Saibokuto on induction of antigen specific IL2 responsiveness was studied. Saibokuto suppressed the induction of IL2 responsiveness induced by Dermatophagoides farinae (Df) antigen in peripheral blood mononuclear cells from patients with bronchial asthma. Saibokuto-pretreated adherent cells failed to present Df antigen to non-adherent responding T cells for induction of their IL2 responsiveness. The same dose of Saibokuto had no impact on non-adherent cells. Saibokuto also suppressed the induced IL2 responsiveness of lymphocytes from the same patients on stimulation wit PPD, but not with Con A. These combined data suggests that Saibokuto has a weak immunosuppressive effect on Df induced IL2 responsiveness of lymphocytes from asthmatic children. Effect of Saibokuto on induction of antigen specific IL2 responsiveness was studied. Saibokuto suppressed the induction of IL2 responsiveness induced by Dermatophagoides farinae (Df) antigen in peripheral blood mononuclear cells from patients with bronchial asthma. Saibokuto-pretreated adherent cells failed to present Df antigen to non-adherent responding T cell for induction of their IL2 responsiveness. Non-adherent cells had no impact by the same dose of Saibokuto. Saibokuto also suppressed the induced IL2 responsiveness of lymphocytes from the same patient on stimulation with PPD, but not Con A. These combined data suggest that Saibokuto has a weak immunosuppressive effect on Df induced IL2 responsiveness of lymphocytes from asthmatic children. Effect of Saibokuto on induction of antigen specific IL2 responsiveness was studied. Saibokuto suppressed the induction of IL2 responsiveness induced by Dermatophagoides farinae (Df) antigen in peripheral blood mononuclear cells from patients with bronchial asthma. Saibokuto-pretreated adherent cells failed to present Df antigen to non-adherent responding T cell for induction of their IL2 responsiveness. Non-adherent cells had no impact by the same dose of Saibokuto. Saibokuto also suppressed the induced IL2 responsiveness of lymphocytes from the same patient on stimulation with PPD, but not Con A. These combined data suggest that Saibokuto has a weak immunosuppressive effect on Df induced IL2 responsiveness of lymphocytes from asthmatic children.

Animals↗
PubMed1990

[Anti-CD45R antibody-treated normal lymphocytes respond to interleukin 2 (IL2) after stimulation by allergens].

Interleukin 2 (IL2) responsiveness was specifically induced by Dermatophagoides farinae (Df) antigen in Df-sensitized lymphocytes from asthmatic children, but not in normal lymphocytes. Df-induced IL2 responsiveness was also observed in normal lymphocytes pretreated (Day 0) with anti-CD45R antibody, which recognize suppressor inducer subset among CD4+ T cells. However anti-CD45R antibody was no longer effective when the lymphocytes were cultured for more than one day with the antigen, suggesting its effect in the initial phase of the reaction. The intensity of the response induced in normal lymphocytes by the anti-CD45R was comparable to that of the patients sensitized to the nominal antigen. The response of the patients was no longer augmented by the anti-CD45R antibody. Taken together, these data suggest that even normal lymphocytes have potentiality to elicit Df-induced IL2 responsiveness and it is probably derepressed by inhibiting suppressor inducer subset with the anti-CD45R antibody. Also suggested is a defective suppressor inducer activity in the lymphocytes which may lead to hyperreactivity to allergens in asthmatic children.

Allergens↗
PubMed1990

[Suppressive effect of azelastine on the induction of Df antigen specific IL-2 responsiveness in lymphocytes from patients with bronchial asthma].

Effect of azelastine on the induction of Dermatophagoides farinae (Df)-antigen specific IL-2 responsiveness of the lymphocytes was examined. Azelastine suppressed the induction of IL-2 responsiveness induced by Df antigen in peripheral blood mononuclear cells from patients with bronchial asthma in a dose dependent manner. Azelastine suppressed antigen presenting adherent cells but not non-adherent responder cells (T cell rich fraction). The antigen specific IL-2 responsiveness induced by purified protein derivative (PPD) in healthy adults was also suppressed by this drug, but not by concanavalin A (Con A). These data suggest that Azelastine suppresses the antigen specific lymphocyte reactions, and that these effects are based on the weak suppressive effect on antigen presenting and/or processing pathway.

Animals↗
PubMed1989

Multiple effects of human recombinant interleukin 4 on human myeloid monocyte cell lines.

The effects of recombinant human interleukin 4 (rIL-4) on proliferation and differentiation on human myeloid/monocytic leukemia cell lines were examined. At high concentrations, rIL-4 had a slight enhancing effect on [3H]thymidine incorporation by U937 cells. rIL-4 markedly induced expression of the Fc epsilon receptor (CD23) and the Leu-M3 antigen (CD14) on U937 cells. HL60 and THP-1 cells treated with rIL-4 also showed increased CD23 expression, but little change of CD14 antigen expression. CD23 induction required lower amounts of IL-4 than needed for T cell growth, indicating that CD23 induction on U937 will serve as a sensitive assay for human IL-4. rIL-4 reduced the steady state level of IL-1 beta mRNA in U937.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

T cells from eosinophilic patients produce interleukin-5 with interleukin-2 stimulation.

Anti-murine (m) interleukin-5 (IL-5) antibody was found to inhibit eosinophil (Eo) colony formation stimulated by recombinant human (rh) IL-5, but did not inhibit the production of Eo stimulated by rh IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF). Conditioned medium (CM) prepared from eosinophilic patients' T cells with interleukin-2 (IL-2) stimulation (T-IL-2-CM), was found to contain CFU-Eo growth-stimulating factor. Using anti-mIL-5 antibody, we demonstrated that T-IL-2-CM from patients with eosinophilia contained a significant amount of IL-5. We also detected IL-5 mRNA in T cells from eosinophilic patients with IL-2 stimulation. These results suggest that IL-5 plays an important role in the induction of selective eosinophilia in humans and that IL-5 is produced from T cells with IL-2 stimulation.

Adult↗
PubMed1989

Expression of different combinations of interleukins by human T cell leukemic cell lines that are clonally related.

We have analyzed expression patterns of 7 lymphokine mRNAs by Northern blot analyses in 19 different human T cell clones derived from patients with adult T cell leukemia. However, we were not able to reveal particular combinations of lymphokine production that allowed classification of human T cells. Especially, four clonally related leukemic lines that were established independently from the same patient with adult T cell leukemia expressed different combinations of lymphokine mRNAs, indicating that the expression of various lymphokines is not fixed but rather variable even among progenies of a single T cell clone.

Clone Cells↗