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Biomedical subjects

T Sakane

Publications and source records attributed to T Sakane.

At least 163 records · Page 9Linked to original sources
PubMed1985

Modulation of the immunoreactivity of a T-lymphocyte subpopulation by neutrophil-released prostaglandin.

The effect of polymorphonuclear leukocytes (PMNs) on lymphocyte subpopulations and their reactivity was investigated by adding supernatants obtained by culturing PMNs with allogeneic or autologous lymphocytes which had been pre-treated with prostaglandin (PG) synthetase inhibitors. PMNs were obtained from 12 healthy individuals, 7 patients with systemic lupus erythematosus (SLE) and 6 patients with bacterial infections. Freshly prepared normal lymphocytes pretreated with PG synthetase inhibitors were incubated with the above supernatants, and the lymphocyte and T-lymphocyte subpopulations were then quantitated, the responses of lymphocytes to mitogens measured and the generation of helper and suppressor T-cell activities for PWM-stimulated cultures assessed. We also ascertained which T-cell population, i.e. OKT4+ or OKT8+ cells, which had been altered by incubation with supernatants, was responsible for the suppressor T-cell activity. A reduced per cent of OKT4+ cells; depressed responses to Con A, PHA, PWM and allogeneic lymphocytes, impaired helper T-cell activity; and increased suppressor T-cell activity were noted after incubation of lymphocytes with supernatants. The percentage of T lymphocytes and of OKT8+ cells was, however, not affected. Further, enhanced suppressor T-cell activity was obtained when supernatant-incubated OKT4+ cells were cultured with OKT8+ cells, regardless of whether the latter had previously been exposed to supernatants. Addition of PG inhibitors to PMN co-cultures nearly restored the original percentage and reactivity of the T-lymphocyte populations, indicating a role for PG released from PMNs in the effects observed. The amount of PG demonstrated in co-culture supernatants was 30 times more than obtained by sonification of fresh PMNs and 10 times more than found in the culture medium containing PMNs alone. These results suggest that, besides monocytes, other phagocytes, including PMNs, can modulate lymphocyte-mediated immune reactivity by the release of PG. Deceased number of OKT4+ cells, impaired helper T-cell activity and enhanced suppressor cell activity may, at least in part, result from the effect of PG released from PMNs as well as monocytes.

Adolescent↗
PubMed1985

Neutrophil-generated active oxygens in linear IgA bullous dermatosis.

To examine the possible correlation between tissue injury and neutrophil-produced active oxygens (AOs) in patients with linear IgA bullous dermatosis (BD), we studied the capacity of neutrophils from six patients with BD to generate AOs. Cultured endothelial cells from human umbilical-cord vein were also incubated with the patients' neutrophils to assess AO-induced tissue injury. The AO production by patients' neutrophils was significantly elevated. The patients' neutrophils, as well as those from healthy controls preincubated with patients' serum, produced significantly increased levels of cytotoxic response on coincubation with chromium 51-labeled human endothelial cells. These results suggest that the tissue damage observed in BD may be partially due to both excessive production of AOs by neutrophils and a serum factor present in the patients, and further postulate the similar pathogenic process in dermatitis herpetiformis.

Adolescent↗
PubMed1985

Characterization of T lymphocyte subpopulations responsible for deficient interleukin 2 activity in patients with systemic lupus erythematosus.

Normal immunoregulation depends on a complex set of cellular interactions in which interleukin 2 (IL 2) appears to play an important role. We have examined the IL 2 activity in patients with systemic lupus erythematosus (SLE). IL 2 production by phytohemagglutinin (PHA)-stimulated T cells for 48 hr was measured by the ability of their culture fluid to induce proliferation of normal human T cells that had been activated for more than 20 days by PHA plus IL 2. To measure IL 2 responsiveness, T cells were blasted by preincubation with concanavalin A for 96 hr and stimulated for another 72 hr with lectin-free standard IL 2. SLE T cells failed to produce normal levels of IL 2 in vitro compared with normal control T cells. This failure resided in both OKT4+ and OKT8+ cells. Furthermore, the abnormality was due neither to soluble inhibitory factors produced by SLE T cells nor to active suppressor cells that might be induced by PHA-stimulation. Responsiveness to IL 2 of T cells from some, but not all, SLE patients was decreased significantly from that of normal controls. Absorption studies as well as studies with anti-Tac antibody demonstrated that the impaired responsiveness of T cells in the specific patients with SLE was due to inadequate expression of IL 2 receptors on the T cells upon activation. This defect was exclusively ascribed to the dysfunction of OKT4+, but not OKT8+, cells. The above defects in production of and responsiveness to IL 2 observed in patients with SLE were present at all times regardless of the disease activity or of corticosteroid therapy. Thus, the deficient IL 2 activity may be intrinsic to SLE lymphocytes and may contribute to impaired immunoregulation and to the development of SLE.

Adult↗
PubMed1985

OKT4+ and OKT8+ T lymphocytes produce soluble factors that can modulate growth and differentiation of human B cells.

The human T cell subset(s) responsible for the production of soluble factors that can modulate B cell growth and B cell differentiation was investigated in the present study. For this purpose, highly purified OKT4+ and OKT8+ lymphocytes were stimulated with phytohaemagglutinin and phorbol myristate acetate. Subsequently, culture supernatants were analysed for B cell growth factor (BCGF) activity and B cell differentiation factor (BCDF) activity in the following systems: 1) maintenance of a proliferative state of Staphylococcus aureus of strain Cowan I (SAC)-stimulated B cells and 2) induction of plaque-forming cell responses of SAC-stimulated B cells. Mitogenic stimulation led to production of equivalent amounts of either BCGF activity or BCDF activity from both of the OKT4+ and OKT8+ subsets. These findings may provide a basis for further studies of the molecular mechanisms as well as cellular interactions involved in human B cell activation, proliferation and differentiation.

Adult↗
PubMed1984

Dissociation of the inhibitory effect of dapsone on the generation of oxygen intermediates--in comparison with that of colchicine and various scavengers.

4,4'-Diaminodiphenyl sulfone (dapsone, DDS) is highly effective in dermatitis herpetiformis and immune complex disease in which polymorphonuclear leukocytes (PMN) play an important role. We studied the dose-response effect of DDS (10-1 mM) on the generation of oxygen intermediates (OI:O2-, H2O2, OH.) and chemiluminescence using PMN and the xanthine-xanthine oxidase system. The effect of colchicine and five oxygen radical scavengers on OI production in both systems was also examined and compared with that of DDS. We found that, except for O2- generation, which was slightly enhanced, DDS decreased the levels of OI measured as effectively as scavengers. Scavengers also capable of degrading OH. and 1O2 markedly reduced the levels of OH. and chemiluminescence while slightly increasing the level of O2-. Therefore, DDS was considered to exert effects similar to H2O2, and OH. and 1O2 scavengers. Colchicine did not decrease OI values produced in the xanthine-xanthine oxidase system but affected PMN-mediated OI generation, possibly by its cytoxic effect. Our results suggest that DDS, in contrast to colchicine brings about rapid clinical improvement in PMN-mediated autooxidative disorders by quenching reactive OI such as H2O2, OH. and chemiluminescence.

Colchicine↗
PubMed1984

Phospholipid transmethylation in the membrane of human neutrophils and lymphocytes.

Phospholipid transmethylation in the microsomal fraction of stimulated and unstimulated human leukocytes was measured in a recently developed assay system. Microsomal fraction was prepared from neutrophils, unseparated lymphocytes, T lymphocytes, and non-T lymphocytes by sonication and subsequent ultracentrifugation. Two hundred micrograms of microsomal protein was reacted with S-adenosyl-L-[methyl-3H]methionine. In unstimulated cells, incorporation of methyl-3H into phospholipid was 0.60 +/- 0.06 pmol min-1 mg protein in neutrophil membrane, 0.84 +/- 0.075 in unseparated lymphocytes, 1.23 +/- 0.17 in T lymphocytes, and 0.71 +/- 0.085 in non-T lymphocytes (mean +/- SE). Stimulation of neutrophils with opsonized zymosan or concanavalin A (Con A), and of lymphocytes with Con A, phytohemagglutinin, or pokeweed mitogen increased 15 to 30%. The resulting methylated phospholipids were identified and quantitated by two-dimensional thin-layer chromatography. The inhibitor 5'-S-isobutyl-5'-deoxyadenosine (SIBA) inhibited transmethylation 47-55%. This assay system appears to measure specifically the activity of methyltransferases which mediate the transmethylation of membrane phospholipid; the assay should find important applications in the study of membrane lipid metabolism in human health and disease.

Chromatography, Thin Layer↗
PubMed1984

Oxygen metabolism in phagocytes of leprotic patients: enhanced endogenous superoxide dismutase activity and hydroxyl radical generation by clofazimine.

We examined the generation of active oxygens (O2-, H2O2, and OH X ) and the superoxide dismutase (SOD) activity of polymorphonuclear leukocytes (PMNs) and monocytes from 14 leprotic patients manifesting a bacillary index above 2.2. Patients with disease of more than 4 years in duration showed significantly enhanced SOD activity and a decrease in O2- and OH X production. The antileprotic agent, clofazimine, significantly increased the generation of OH X in a dose-dependent manner, with a subsequent decrease in H2O2, but had no effect on the SOD activity of the PMNs and monocytes. In medium containing FeSO4 or Fe2+-EDTA, the drug elevated OH X production markedly further. Phagocytic SOD in PMNs and monocytes of leprotic patients was both host and bacillus derived, because the presence of cyanide, to which human-derived cuprozinc SOD is susceptible, did not completely abrogate SOD activity. The difficulty in treating leprosy may be partly ascribable to decreased phagocytic OH X generation, which in leprosy patients is apparently due to the uptake of Hansen bacillus-derived SOD. Clofazimine may be effective in leprosy by chelating Fe2+, with the resultant potentiation of the catalyzing activity of Fe2+ in the Haber-Weiss reaction increasing OH X formation from H2O2.

Adult↗
PubMed1984

Role of stimulated neutrophils from patients with systemic lupus erythematosus in disturbed immunoreactivity, with special reference to increased oxygen intermediates generated by the neutrophils.

Zymosan-stimulated neutrophils from 6 patients with untreated, active systemic lupus erythematosus (SLE), from patients with bacterial infections, and from healthy controls, were studied for production of oxygen intermediates (O-2, H2O2, OH . and chemiluminescence) and lysosomal enzymes. Oxygen intermediate production was highest in neutrophils from active SLE patients, while lysosomal enzyme release was highest in neutrophils from patients with bacterial infections. SLE neutrophils, upon culture with autologous or normal lymphocytes, markedly reduced the number of surviving OKT4+ cells and the proliferative response of the surviving cells to mitogens; a reduction was also observed amongst the surviving lymphocytes in the proportion of total T cells and OKT8+ cells, and in the generation of Con A induced suppressor activity. When superoxide dismutase and catalase were included in the neutrophil-lymphocyte co-cultures, the number of T- and OKT8+ cells, and the suppressor activity were restored but not completely (60-75%), the lymphocyte mitogenic response and number of OKT4+ cells were less well restored (40-50%). When lymphocytes were co-cultured with neutrophils from healthy or infected subjects, there was a mild decrease in mitogenic responses and OKT4+ cells, while the suppressor T-cell activity was markedly enhanced. These results were not affected by scavengers. These results suggest that in SLE, reduced T-lymphocyte subpopulations and altered immunoreactivity may be partially due to excessive production of oxygen intermediates and probably other factors by stimulated neutrophils; these results further suggest that in all the subjects, diseased or healthy, neutrophils generate unidentified factors other than oxygen intermediates that reduce the generation of OKT4+ cells and lymphocyte mitogenic responses, and that potentiate suppressor T-cell activity.

Adolescent↗
PubMed1984

Decrease in generation of reactive oxygen species by neutrophils from patients with infectious mononucleosis: role of suppressor T lymphocytes.

We assessed the generation of reactive oxygen species (ROS: O2-, H2O2, OH . , chemiluminescence) by neutrophils and monocytes from six patients with infectious mononucleosis, ten patients with other viral diseases, and ten normal controls. Neutrophils from infectious mononucleosis patients showed markedly decreased generation of all reactive oxygen species, compared with the two control groups; this abnormality persisted for four to eight weeks after disease onset. Monocytes from these patients generated normal levels of ROS. Normal neutrophils incubated with T lymphocytes from infectious mononucleosis patients generated significantly less of each ROS than did those incubated with T cells from either control group. T cell-mediated suppression of ROS generation required both OKT4+ cells from infectious mononucleosis patients and OKT8+ cells from either patients or normals. We conclude that the generation of reaction oxygen species in neutrophils is suppressed in patients with infectious mononucleosis, at least in part, by interacting subsets of T lymphocytes.

Adolescent↗
PubMed1984

Activation of immune regulatory circuits among OKT4+ cells by autologous mixed lymphocyte reactions.

We examined the nature of an autologous mixed lymphocyte reaction (AMLR) using T cell subsets defined by monoclonal antibodies. Cells capable of proliferating in the AMLR were demonstrated to reside in an OKT4+, but not an OKT8+, cell subset. With regard to the role of the T cell subsets recoverable from AMLR in the immune regulation, OKT4+ cells isolated from cells that had been activated for 3 days in AMLR did help pokeweed mitogen (PWM) stimulated immunoglobulin synthesis by autologous B cells. However, the OKT4+ cells activated for 6 days in AMLR exerted strong suppressor activity for PWM-induced immunoglobulin synthesis. Irradiation with 1,500 rad on activated OKT4+ cells in AMLR for 6 days not only eliminated the suppressor function but allowed for re-emergence of helper function. Cells exerting suppressor activity alone were recovered from OKT8+ cells stimulated with or without autologous non-T cells. These data suggest that OKT4+ cells activated in AMLR contain two functionally different subsets; one as helper cells and the other as suppressor cells. In addition, the emergence of OKT4+ suppressor function follows activation of the OKT4+ helper population, suggesting that a part of AMLR reflects a mechanism of 'feedback suppression' among OKT4+ cells.

Antibodies, Monoclonal↗