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Biomedical subjects

J Yata

Publications and source records attributed to J Yata.

At least 55 records · Page 3Linked to original sources
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

Pulmonary miliary tuberculosis and T-cell abnormalities in a severe combined immunodeficient patient reconstituted with haploidentical bone marrow transplantation.

We report the development of miliary tuberculosis in a 7-year-old boy with severe combined immunodeficiency (SCID), whose immune system had been only partially reconstituted by haploidentical bone marrow transplantation. Although alpha beta and gamma delta T cells were of donor origin, alpha beta T cells in this patient showed defective interleukin-2 (IL-2) production, impaired IL-2 responsiveness and decreased cytolytic activity. However, gamma delta T cells could exhibit enough cytolytic activity after incubation with IL-2. Despite the presence of disseminated infection, C-reactive protein (CRP) remained negative. IL-2 therapy aggravated the disseminated tuberculosis though gamma delta T cells were supposed to be activated, and concurrently CRP became positive. These findings suggest that gamma delta T cells have no more than limited immunological roles in mycobacterium tuberculosis infection.

Bone Marrow Transplantation↗
PubMed1994

[Mechanisms of the intractability of bacterial infections in immunodeficiency status in childhood].

Most of the primary immunodeficiency diseases develop in childhood. The patients with antibody deficiency are susceptible to pyogenic bacteria since antibody is essential to opsonize bacteria. T cell deficiency causes defect of cytokine production needed to activate macrophages to kill intracellular bacteria such as mycobacteria and leeds to intractable infection of such bacteria. Complement mediated bacteriolysis is important to protect neisseria such as meningococcus and deficiency of C5-C9 provides susceptibility to the bacteria. Defect of superoxide synthesis or adhesion of neutrophils is related to severe infection of pyogenic bacteria. On the way of development of immune system, children especially in early infancy display susceptibility to bacterial infections.

Age Factors↗
PubMed1993

Increased urinary excretion of human cytomegalovirus in children with malignancy: detection by polymerase chain reaction.

Human cytomegalovirus (HCMV) is one of the most important agents causing opportunistic infections in immunocompromised hosts. In this study, we examined the urinary excretion of HCMV in children with malignancy using polymerase chain reaction (PCR). Urine samples were collected from on-therapy, off-therapy patients with malignancy, and healthy controls. A simple DNA extraction method using glass powder was employed, and inhibitory effect of urine on PCR was prevented. For PCR, a pair of primers from the HCMV major immediate early gene sequence was used. Among patients who received intensive chemotherapy, 52.0% had urinary HCMV excretion after the chemotherapy course. In contrast, off-therapy patients and healthy controls showed a lower incidence of urinary HCMV excretion (20.4 and 8.7%, respectively). The incidence of HCMV urinary excretion in the on-therapy group was significantly higher than healthy controls (P < 0.05). In the on-therapy group, the total white blood cell count of the virus excreters was lower than that of non-excreters. The incidence of HCMV excretion was high in on-therapy patients. Most of the virus excreters were seropositive, so their viruria was thought to be caused by reactivation. Repeated monitoring of virus excretion by this rapid and simple method may be useful to detect HCMV infection early and to control it in such patients.

Adolescent↗
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↗
PubMed1992

Measurement of beta 2 microglobulin in dried urine spotted on filter paper by means of a forward sandwich enzyme-linked immunosorbent assay.

We devised a highly sensitive forward sandwich enzyme-linked immunosorbent assay (ELISA) for estimation of the beta 2-microglobulin concentration in dried urine spotted on filter paper. This method is suitable for mass screening because of the good reproducibility, satisfactory stability, low operation cost and easy sample collection. However, preliminary studies using our new method for detecting renal diseases in the Tokyo infant population did not produce good results. The high cut-off value may have been the main reason. To make this ELISA more suitable for mass screening, we plan to reduce the cut-off value, test older children and improve the extraction step.

Enzyme-Linked Immunosorbent Assay↗
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

Characterization of human thymic lymphocytes forming rosettes with stromal cells.

The interaction of thymic lymphocytes and stromal cells is believed to be important for T cell development in thymus. In this study, thymic rosettes (TR), which are cell-cell complexes of thymic lymphocytes and stromal cells, were isolated from human thymic tissue, and were characterized. Treating human thymus with collagenase in mild condition, human TR were successfully isolated. Subsequently, TR were purified by the 1G sedimentation method. Human TR consisted of a stromal cell in center surrounded by lymphocytes. The stromal cells were positive for CD14, CD11b, and HLA-DR but negative for thymic epithelial cell specific mAb, UH-1, suggesting that they are macrophage/dendritic cells. The lymphocytes which formed TR (TRL) were mainly double positive (CD4+CD8+) and CD1+ cells, and few of them expressed bright CD3, indicating that TRL are in the intermediate maturation stage. TRL expressed activation markers (Ta1 and HLA-DR) in a significantly higher percentage of cells than did unselected thymocytes. Blocking test revealed that CD11a and CD2 are involved in the binding of TRL and the stromal cells as adhesion molecules.

Antigens, Surface↗
PubMed1992

[Cytokine therapy of immunodeficiency].

The cellular immunodeficiency diseases especially those with impaired IL-2 production are successfully treated by every day injection of rhIL-2. IL-2 is also effective on some patients with antibody deficiency probably caused by the lack of T cell help for B cells. Prolonged infection of EB-virus, human immunodeficiency virus, fungi and mycobacteria can be ameliorated by IL-2 treatment. Superoxide production and bacteriocidal activity of the leukocytes from some cases of chronic granulomatous disease are improved by injection of interferon gamma. Succeeding injection of G-CSF is effective to maintain the leukocyte count of congenital neutropenia to the level competent to protect bacterial infections.

Agammaglobulinemia↗
PubMed1992

Peroxidase-negative and myelomonocytic antigen-positive acute leukemia.

Between 1983-1988 bone marrow samples obtained from 195 peroxidase-negative leukemia patients were analyzed for their surface antigens. Thirteen of these patients (6.7%) had myelomonocytic-positive and lymphoid-negative antigens. These leukemic cells reacted with CD13 in eight patients, CD33 in seven, CD11 in six and CDw41 in two. In none of these patients did the leukemic cells react with CD1, CD2, CD3, CD4, CD5, CD8, CD10, CD19 or CD20. Leukemic cells from two patients were reactive with CD7. These leukemic cells demonstrated L2 morphology in 11 patients and L1 morphology in one patient. The leukemic cells from the final patient were diagnosed as those of leukemic transformation of myelodysplastic syndrome. Chromosomal abnormality was observed in approximately half of the patients examined (6/10). Cytochemical analysis revealed that the leukemic cells were negative for periodic acid Schiff stain but positive for acid phosphatase. The prognosis of these patients was markedly poor as compared to acute lymphocytic leukemia or typical peroxidase-positive nonlymphocytic leukemia. Complete remission was induced in only 30% of patients and duration of survival was short (4.7 months). This suggests that myelomonocytic antigen-positive peroxidase-negative acute leukemia is a distinct type of leukemia and may require more aggressive therapy to improve survival.

Acid Phosphatase↗
PubMed1992

Reversible G1 arrest induced by dimethyl sulfoxide in human lymphoid cell lines: kinetics of the arrest and expression of the cell cycle marker proliferating cell nuclear antigen in Raji cells.

In order to elucidate further the mechanism of reversible cell cycle arrest induced by treatment of Raji cells with 1.5% dimethyl sulfoxide (DMSO), we have performed a detailed analysis of the kinetics of arrest and of reentry into the cell cycle after removal of DMSO and have correlated cell cycle progression with expression of proliferating cell nuclear antigen (PCNA). No significant effect of DMSO on cell cycle patterns, assessed by flow cytometric analysis of bromodeoxyuridine-prelabeled cells, was seen for the first 19 h of treatment. A clear reduction of entry into S phase was detected by about 25 h of treatment; essentially all cells were arrested with a G1 content of DNA after 96 h of treatment. When DMSO-arrested cells were released from the block, entry into S phase began at 12 h after release and continued in a fairly asynchronous manner for a further 12-14 h. In arrested cells, the content of PCNA was reduced to about 25% of the amount present in logarithmically growing G1 phase cells. Six h after release from DMSO, PCNA RNA transcripts were first detected by Northern blotting. The increase of PCNA protein, detected by Western blotting, was seen by 9 h after release. The kinetics of entry into the cell cycle and restoration of PCNA protein are similar to that seen in serum stimulation of quiescent cells. These results suggest that DMSO reversibly arrests proliferation of Raji cells at G0 or at an early point in G1 phase and that progression through late G1 phase and entry into S phase are correlated with synthesis of the PCNA gene product.

Antigens, Neoplasm↗
PubMed1991

Effect of recombinant interleukin 5 on the generation of cytotoxic T cells (CTL).

The effect of recombinant human interleukin 5 (rhIL5) on the generation of CTL was investigated by using autologous EBV-transformed B cells as the target. Exogenous IL5 augmented the CTL generation, and its effect was most active at the concentration of 10 ng/ml, and when added at the late phase of culture in this system. IL5 augmented specific CTL activity rather than MHC nonrestricted CTL activity as detected with K562 and Daudi when compared to that augmented by IL2. IL5 did not increase the expression of p55 or p75 IL2R nor the responsiveness to IL2. Taken together with the finding that IL5 augmented the CTL activity even in the presence of cyclosporin A, the effect of IL5 on the CTL generation seems not to act through the IL2-IL2R system.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Increase of ovalbumin (OVA)-specific B cells in the peripheral blood of egg-allergic patients.

Allergen-specific B cells were detected by antigen-coated magnetic beads. The frequency of ovalbumin (OVA)-specific B cells was significantly higher in patients with egg white-allergy than in age-matched nonallergic individuals. These B cells, isolated by the immunomagnetic-beads method, produced anti-OVA antibodies of mostly IgM class when they were transformed by Epstein-Barr virus and cultured for about 2 weeks. Based on a chronologic analysis, the increase of OVA-specific B cells was found to precede the increase of IgG and IgE anti-OVA antibodies in the serum. These observations indicated that OVA-binding B cells in the peripheral blood are already committed to producing IgM antibody and probably are the precursors of antibody-forming cells of the IgG or IgE class.

Adult↗
PubMed1991

A B cell line from a patient with pure red cell aplasia produces an immunoglobulin that suppresses erythropoiesis.

A 4-year-old boy with pure red cell aplasia was investigated. Immunophenotypic analysis of peripheral blood lymphocytes revealed a marked increase of CD20+ cells, which fell from 25.9% in the active stage to 9.7% in remission. The plasma contained a suppressive activity against CFU-e and BFU-e formation by the patient's bone marrow cells, which disappeared when the disease went into remission. Prednisone (2 mg/kg/day) therapy was tried for 5 weeks, but produced no improvement. Subsequently, high-dose gamma-globulin therapy induced complete remission of anemia. A lymphoblastoid B cell line obtained from the patient before therapy produced a factor that suppressed erythropoiesis but not granulopoiesis. The suppressive activity resided in the immunoglobulin fraction and was adsorbed by an anti-immunoglobulin column. These results indicate that expansion of B cells producing an immunoglobulin which suppressed erythropoiesis was involved in the pathogenesis of the disease in this patient.

B-Lymphocytes↗
PubMed1991

Generation and function of gamma delta T cells after allogeneic bone marrow transplantation in humans: comparison in absence or presence of HLA-matched or mismatched thymus.

We have observed two patients who exhibited an exclusive increase of delta TCS1+ subset of gamma delta T cells in the peripheral blood after bone marrow transplantation (BMT). In one case with severe combined immunodeficiency (SCID) who received haploidentical BMT from his father, gamma delta T cells appeared only after thymus transplantation. However, his T cell-mediated immunity remained severely defective despite the generation of T cells of donor origin. In the other case with aplastic anemia, delta TCS1- gamma delta T cells began to increase in the peripheral blood later. This indicates that the thymus is necessary for the generation of gamma delta T cells and that the delta TCS1+ subset is dominant in the early stages of their ontogeny. delta TCS1+ T cell lines were established from both patients, and allo-reactivity was investigated. The cell line from the latter case reacted to recipient cells in a mixed lymphocyte reaction, but did not show cytotoxity to the allogeneic cells including recipient cells. The other cell line, from the former case, did not react to either donor or recipient cells. This indicates that an intact thymus is needed for gamma delta T cells to acquire allo-reactivity. Both cell lines showed MHC non-restricted cytotoxity against NK-sensitive target cells.

Adolescent↗
PubMed1990

Phenotypic profile and functions of T cell receptor-gamma delta-bearing cells from patients with primary immunodeficiency syndrome.

TCR-gamma delta-bearing T cells have been reported to be increased in several immunodeficient patients. However, their functional role and phenotypic characterization have not yet been well documented. In this study we examined the surface phenotypes and functional properties of TCR-gamma delta+ cells from several patients with primary immunodeficiency syndrome. It was demonstrated that TCR-gamma delta+ cells detected by TCR-delta 1 mAb were increased in some of the patients, particularly in patients with Wiskott-Aldrich syndrome and severe combined immune deficiency. The TCR-gamma delta+ cells showed such a unique profile that more than 60% of the cells expressed delta-TCS1, which is normally present in a lesser amount, and that most of the cells lacked CD5 T lineage marker. TCR-gamma delta+ cells from the patients with primary immunodeficiency syndrome served as NK cells as observed in normal individuals, while displaying weak LAK and allogeneic cell-specific killer activities. The TCR-gamma delta+ cells were classified into several subpopulations according to their antigenic phenotype, then their NK activity of normal individuals and patients, lymphokine-activated killer and allo-specific killer activities of normal individuals were compared among the subpopulations. Delta-TCS1+ cells mediated almost the same killer activities as total TCR-gamma delta+ cells, whereas CD8+ TCR-gamma delta+ cells displayed stronger cytotoxic activities in both normal subjects and the patients with primary immunodeficiency syndrome.

Antibodies, Monoclonal↗
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↗