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O Saiki

Publications and source records attributed to O Saiki.

At least 37 records · Page 2Linked to original sources
PubMed1987

Age-related changes of the function of T cell subsets: predominant defect of the proliferative response in CD8 positive T cell subset in aged persons.

The proportion of CD8 positive cells in the peripheral blood AET-rosette forming T cells from aged persons was significantly reduced than that from young persons. The difference in the proportion between aged and young groups became more significant after proliferative response to a mitogen phytohemagglutinin (PHA) or a specific antigen tuberculin active peptide (TAP). The purified macrophage-deprived T cells (Twp), CD4 (T4) positive cells or CD8 positive cells were prepared from aged or young persons. These cell preparations lost proliferative response to PHA or TAP but showed marked proliferative response to the combined stimulation to 1 microM of ionomycin and 1 nM of phorbol-12-myristate-13-acetate (PMA) at usual culture cell density (2.5 X 10(5)/ml). Proliferative responses of these cell preparations to the combined stimulation were significantly reduced in the aged than those in the young and the magnitude of the difference in the proliferative responses between aged and young groups was more pronounced in CD8 positive cell population than in CD4 positive cell population. Although the cell preparations were relatively independent of exogenous IL-2 for the proliferative response to the combined stimulation of ionomycin and PMA at usual culture cell density, they needed exogenous IL-2 for sustained proliferation at lower culture cell density (5 X 10(3)/ml). These IL-2-dependent proliferative responses to the combined stimulation in the aged were significantly lower than those in the young and again the difference in the proliferative magnitude between aged and young groups was greater in CD8 positive population. The mechanism(s) of age-related change of the proportion and proliferative ability of T subsets were discussed.

Adult↗
PubMed1987

Age-associated changes in proliferative and differentiative response of human B cells and production of T cell-derived factors regulating B cell functions.

The abilities of highly purified B cells to repeat replication for clonal expansion and to differentiate into immunoglobulin secreting cells (ISC) were examined in the aged and young groups. B cells from the aged showed twofold less proliferative response to B cell mitogen Cowan 1 (SAC) than those from the young. The original clone size of SAC responding B cells determined by colchicine block and [3H] thymidine [( 3H] TdR) uptake was not significantly reduced in the aged whereas the ability to repeat replication to expand clonal size was significantly reduced. B cells from aged and young persons were induced into ISC by combined stimulation with SAC and partially purified B cell differentiation factor (BCDF) free of IL-2 activity. ISCs for IgG and IgA were rather increased or at least not reduced in number in the aged as compared with those in the young. We also determined the IL-2 and BCDF activity produced by T cells from aged and young persons. Upon PHA stimulation, the aged T cells produced tenfold less IL-2 activity and threefold higher BCDF activity than did young T cells. Approximately threefold increase in spontaneous secretion of BCDF activity by aged T cells was found as compared with young T cells. The inverse correlation between the IL-2 activity and BCDF activity was found when both activities were determined in the same samples.

Adult↗
PubMed1986

Mechanisms of age-related decline in antigen-specific T cell proliferative response: IL-2 receptor expression and recombinant IL-2 induced proliferative response of purified Tac-positive T cells.

Proliferative response of T cells from aged persons was significantly reduced to a specific antigen tuberculin-active peptide (TAP) determined by [3H]TdR uptake and FCM in comparison to that from the young. Cytokinetic analysis for the proliferative response to TAP showed that, in the aged, the clonal size or the number of the first generation responding cells to TAP was not significantly reduced but the ability to repeat replication was more profoundly affected. Neither the delayed entry into the cell replication nor prolongation of the cell cycle time could explain these results. Similar results have been reported on the proliferative response of T cells to mitogen: PHA (Phytohemagglutinin). Expression of Tac-antigen on T cells determined by anti-Tac antibody binding with FACS after stimulation with either TAP or PHA was found to be reduced significantly in the aged. Both the numbers of high and low affinity IL-2 receptors determined by radiolabelled IL-2 binding assay were also reduced in the aged, but the degree of reduction in number of high affinity ones was more pronounced than that in low affinity ones. Tac-positive T cells were isolated with the use of anti-Tac rosette methods and stimulated with recombinant IL-2 (r-IL-2). Their proliferative response was significantly lower in the aged than that in the young at any concentration of r-IL-2 examined. The number of the first generation responding cells to r-IL-2 in purified Tac-positive T cells from the aged was 82% of that from the young whereas the proliferative response by aged T cells was 39% of that by young ones when the cells were allowed to repeat replication for 3 days. The mechanisms of these multifactorial defects in proliferation of T cells from aged persons were discussed.

Adult↗
PubMed1985

Rescue of IgM, IgG, and IgA production in common varied immunodeficiency by T cell-independent stimulation with Epstein-Barr virus.

We previously defined three categories of B-cell defects in common varied immunodeficiency (CVI): failure to produce IgG and IgA in response to T cell-dependent (TD) stimulation by Staphylococcus bacteria (Sac) plus pokeweed mitogen or B-cell inducing factor (BIF), failure to produce any immunoglobulin, and failure of Sac-induced proliferation and differentiation. The present study includes the responses of 22 CVI patients to T cell-independent (TI) stimulation by Epstein-Barr virus (EBV). In the majority of patients, EBV-stimulated B cells showed normal proliferation and IgM production. In addition, IgG and IgA production was in the range of that for EBV-stimulated normal cells in many patients. Among 11 patients with no TD production of immunoglobulin of any isotype, two showed normal IgM secretion in response to EBV and five others had significant but subnormal responses. Four patients never had humoral responses despite repeated testing and removal of potentially suppressing T cells and monocytes. Concanavalin A stimulation of the T cells from all the patients tested resulted in the production of B-cell inducing factor at higher levels than for normal donor T cells, as assayed on normal Sac-stimulated B cells. These results show that many cases of B-cell defects in CVI patients involving TD production of IgM, switching to TD production of IgG and IgA, and mitogen responses to Sac are not absolute defects. The B cells will respond normally to some stimuli.

Adolescent↗
PubMed1985

Spontaneous immunoglobulin A secretion and lack of mitogen-responsive B cells in systemic lupus erythematosus.

In an analysis of lymphocyte functions of systemic lupus erythematosus (SLE) patients, B cell abnormalities such as a lack of mitogen-responsive B cells and a predominance of spontaneous IgA-secreting cells (SC) were found. Lymphocyte functions of 20 SLE patients were studied. Impaired proliferative response to B cell mitogen, Staphylococcus aureus strain Cowan I (Cowan I), was observed, whereas the response to T cell mitogen phytohemagglutinin was normal. High levels of spontaneous IgA-SC were observed in SLE patients (greater than 10(2) cells/10(4) peripheral blood mononuclear cells [PBMC]), whereas spontaneous IgM-, IgG-, or IgE-SC were not proportionately increased. The number of spontaneous IgA-SC decreased with time in culture and became undetectable by day 5 of culture. In contrast, spontaneous immunoglobulin- (IgM, IgG, and IgA) SC were not observed in healthy volunteers (less than 10 cells/10(4) PBMC). Moreover, in SLE patients failure of induction of immunoglobulin-secreting cells (ISC) was observed when B cells were stimulated by Cowan I and B cell differentiation factor at any day tested, whereas ISC were induced in healthy volunteers on day 6 of culture. Depletion of T cells or macrophages did not affect the results obtained. These results suggest that the abnormalities observed in SLE B cells are not due to the in vitro direct effects of suppressor macrophages or suppressor T cells, and that the condition of the predominance of spontaneous IgA-SC and the unresponsiveness to exogenous stimulation may be emblematic of hyperactive B cells in SLE.

Antibody-Producing Cells↗
PubMed1985

Effect of B cell differentiation factor (BCDF) on biosynthesis and secretion of immunoglobulin molecules in human B cell lines.

Stimulation of human B lymphoblastoid cell lines, CESS and SKW6-CL4 with BCDF induced an increase in IgG- and IgM-secreting cells, as well as a slight increase in IgG and IgM expression on their respective surfaces. Biosynthetic labeling demonstrated that BCDF stimulation induced an increase in synthesis of secretory gamma- and mu-chains, as well as their precursors. A slight but significant increase in synthesis of membrane-bound gamma- and mu-chains and their precursors was also observed by BCDF stimulation. However, an increase in synthesis of secretory heavy chains was much higher than that in membrane-bound heavy chains in both cell lines. Pulse-chase experiments showed that increased synthesis of secretory heavy chains was not due to a decrease in degradation. BCDF stimulation induced a preferential increase in mRNA specific for secretory gamma- and mu-chains in CESS and SKW6-CL4 cells, respectively. These results suggest that BCDF induces an increase in the level of mRNA specific for secretory heavy chains, and then induces final maturation of B cells into immunoglobulin-secreting cells.

Antibody-Producing Cells↗
PubMed1984

Dissociation in the production of B cell-stimulating factors (BCGF and BCDF) and interleukin 2 by T cells from a common variable immunodeficient patient.

In the course of an analysis of lymphocyte functions of common variable immunodeficiency patients, we found one patient whose T lymphocytes released B cell differentiation factor (BCDF) and B cell growth factor (BCGF) without IL 2 production upon stimulation with Con A. The patient was a 68-yr-old woman with hypo-gamma-globulinemia (IgM: 31 mg/dl, IgG: 223 mg/dl, IgA: 23 mg/dl); she suffered from cryptococcal meningitis and pulmonary tuberculosis with a negative result of skin tests to PPD and cryptococcal antigen. The number of T cells and the ratio of T cell subsets (Leu-2a and Leu-3a) was normal. T cells showed no proliferative response to Con A and a low response to PHA (one-tenth of normal response). The addition of patient T cells to normal T cells did not inhibit the proliferation of normal T cells when stimulated by Con A. The culture supernatant of Con A-stimulated T cells contained no IL 2 activity when assayed by an IL 2-dependent T cell line. Expression of Tac antigen was not impaired by Con A stimulation and the addition of partially purified IL 2 from the supernatant of Jurkat T cell line-induced proliferation of Con A-stimulated T cells, indicating that the defect observed was not in IL 2-responding cells but in IL 2-producing cells. In contrast, the culture supernatant of the T cells stimulated by Con A or PHA contained BCDF activity as much as that of normal T cells when assayed by Cowan I-stimulated normal B cells or the B lymphoblastoid cell line SKW6-CL4. The supernatant also contained BCGF activity. These results suggest that B cell-stimulating factor (BCGF, BCDF) and IL 2 may be synthesized by different subsets of T cells or that the synthesis of those lymphokines are independently regulated in the same cells.

Adult↗
PubMed1983

IgM and IgG secretion in human B-cell lines regulated by B-cell-inducing factors (BIF) and phorbol ester.

Human B-cell lines were screened for stimulation of immunoglobulin production by incubation with lymphokine (LK) or tumor promoter, phorbol myristic acetate (PMA). One group of lines had essentially no immunoglobulin-secreting cells (ISC) under any condition (less than 0.01%), detected by a reverse plaque assay. Another group of lines had high levels of ISC (greater than 5%) which was not increased substantially by inducing agents. In a third group of IgM and IgG lines, there were intermediate levels of ISC which could be increased by LK, PMA or both agents. No evidence for isotype switching in a number of stimulated IgM and IgG cell lines was detected. Clone SKW6.4 of an IgM line was highly responsive to a B-cell-inducing factor (BIF) in LK. BIF for SKW6.4 and IgG line ARH-77 was weakly binding to DEAE cellulose, about 20,000 mol. wt., and separable from IL-2 by blue agarose chromatography. IL-2 did not stimulate secretion in SKW6.4 with or without purified BIF. In Clone SKW6.4, BIF stimulated ISC per recovered cell up to 30-fold by day 1 of culture, and these plateau levels of about 6% ISC were maintained for longer than 4 days. Treatment of cells with BIF for less than 1 day was sufficient to produce maximum effect on this clone for the succeeding 4 days. Cells stimulated with BIF and then subcultured at day 3 without BIF showed ISC numbers increasing but at a slower rate than the total population, suggesting that the induced differentiation state is long-lived (half-life of % ISC greater than 6 days) and that ISC produce some daughter ISC.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1982

IgM- and IgD-bearing peripheral blood lymphocytes differentiate to IgM but not IgG or IgA immunoglobulin-secreting cells.

Human peripheral blood mononuclear cells were depleted of surface IgM+ or IgD+ cells and assayed for mitogen-induced differentiation to immunoglobulin-secreting cells (ISC) of IgM, IgG and IgA classes. Stimulatory agents included T cell-dependent pokeweed mitogen, B cell mitogen Staphylococcus aureus bacteria strain Cowan I, and a combination of the two which gives uniform, high levels of ISC from all normal donors. Depletion of either IgM- or IgD-bearing B lymphocytes resulted in loss of cells bearing the other Ig class and blocked most of the mitogenic reactivity to anti-IgM and anti-IgD. Proliferative responses to Cowan I in these depleted populations were about 20% that of unfractionated mononuclear cells. Depletion of T cells increased the mitogenic response to Cowan I and to the two antibody preparations, showing that they are T-independent mitogens. Depletion of IgD+ cells caused partial loss of mitogen-induced IgM ISC (22%-60% of unseparated controls) but no loss of IgG or IgA ISC. Depletion of IgM-bearing cells caused complete loss of IgM ISC, but no loss of IgG or IgA ISC. We previously demonstrated that anti-IgM ISC, but no loss of IgG or IgA ISC. We previously demonstrated that anti-IgM antibody blocked mitogen induction of Ig secretion of these three classes in spleen cells, but only IgM secretion in blood mononuclear cells. Together, the results suggest that the majority of cells in normal blood responding to mitogens to mature to IgG or IgA production belong to IgM-, IgD- B cell subjects, in contrast to precursors of secreting cells for these isotypes in the spleen. Thus, these blood precursors appear to be more mature than the corresponding spleen cells.

Antibodies, Anti-Idiotypic↗
PubMed1982

Three distinct stages of B-cell defects in common varied immunodeficiency.

B-lymphocyte function of 15 patients with primary common varied immunodeficiency or related disease were examined. All patients had low serum levels of IgM, IgG, and IgA, but 12 of 15 patients had nearly normal numbers of peripheral blood B lymphocytes. Mononuclear cells and B cells from peripheral blood were assayed for B-cell mitogenic responses to anti-Ig mu chain antibodies or to Staphylococcus aureus strain Cowan I (referred to as Cowan I), and for differentiation to Ig-secreting cells of IgM, IgG, and IgA classes in the presence of Cowan I and pokeweed mitogen or T-cell factor. The patients all showed profound B-cell defects in one or more of the assays and could be divided into three approximately equal groups based on their responses. The first group showed normal proliferation in response to the two B-cell mitogens and near normal numbers of IgM-secreting cells but no IgG- or IgA-secreting cells. B cells in the second group showed proliferative responses to Cowan I or anti-mu, but no differentiation to Ig-secreting cells. The third group had no B-cell proliferative responses or differentiation in our assays. In several patients from each group, (i) helper T cells were functional in Ig-secreting-cell responses with purified normal B cells, (ii) patient T cells did not significantly suppress formation of Ig-secreting cells by normal cells in coculture, and (iii) removal of T cells with addition of T-cell-replacing factor, or partial removal of monocytes, did not alleviate any of the defects. These studies show that primary B-cell defects in common varied immunodeficiency occur at several levels, probably representing blocks at different stages of differentiation.

Adolescent↗
PubMed1981

Synergistic effects of human B and T lymphocyte mitogens induce uniform, high levels of immunoglobulin secretion among normal donors.

Synergistic effects of B-cell mitogen Staphylococcus bacteria strain Cowan I (Cowan I) plus T-cell activator pokeweed mitogen (PWM) in generating immunoglobulin-secreting cells (ISC) from human peripheral blood mononuclear cells (MNC) were investigated. ISC were assayed by reverse plaque-forming cells uing protein A-coated red blood cells. Low concentrations of PWM plus Cowan I gave superadditive effects on ISI induction, generating 3-20 times as many ISC as optimal amounts of either mitogen alone. The mitogens together and separately showed similar kinetics of ISC; synergy was observed at every day tested. IgM ISC represented 10% of initial MNC from all cell donors tested even if the donors were low responders to either mitogen alone. The numbers of ISC obtained are higher than previous reports and more uniform among donors, making this a superlative method for studies on normal human immunoglobulin secretion.

Antibody-Producing Cells↗
PubMed1981

Induction of human immunoglobulin secretion. I. Synergistic effect of B cell mitogen Cowan I plus T cell mitogens or factors.

Synergistic effects of B cell mitogen Staphylococcus bacteria strain Cowan I (Cowan I) plus T cell mitogens in generating immunoglobulin-secreting cells (ISC) from human peripheral blood mononuclear cells (MNC) were investigated. ISC were assayed by reverse plaque-forming cells with protein A-coated red blood cells. Low concentrations of pokeweed mitogen (PWM) plus Cowan I gave superadditive effects on ISC induction, generating 3 to 10 times as many ISC as optimal amounts of either mitogen alone. The mitogens together and separately showed similar kinetics of ISC; synergy was observed at every day tested. Plaque-forming cells of IgM, IgG, and IgA classes all showed strong synergy, together routinely representing 20% of initial MNC. At day 7 of culture, over 80% of non-E-rosetting cells were ISC. Cell donors tested gave these strong responses even if they were low responders to either mitogen alone. Cowan I plus other T cell mitogens, PHA, Con A, and protein A, also provided good signals for B cell activation. Cowan I induced marked proliferation of purified B cells, but T cell-helper signals were required for differentiation to ISC. T cell-helper factor, induced by PWM or PHA, also showed synergistic effects with Cowan I in induction of ISC. Purified B cells did not respond to T cell-helper factor(s) alone to proliferate or differentiate to ISC. These results indicate that optimal ISC induction occurs with a B cell mitogen plus T cell signals acting synergistically.

Antibody-Producing Cells↗
PubMed1980

Depressed immunological defence mechanisms in mice with experimentally induced diabetes.

Persistent diabetes mellitus with marked hyperglycemia was induced in mice by the administration of streptozotocin. In these streptozotocin-induced diabetic mice, resistance to tubercle bacillus challenge and primary as well as secondardy humoral immune responses against foreign erythrocytes were markedly depressed. The T-cell function in delayed hypersensitivity to 2,4-dinitro-1-fluorobenzene and bacterial phagocytic activity or peritoneal macrophages were markedly depressed. In contrast, the B-cell function in antibody production against T-independent antigen and the intracellular killing of bacteria in peritoneal macrophages were intact. We concluded that depression of the T-cell function or the phagocytic activity of macrophages or both may be the main immunological defect in these mice.

Animals↗
PubMed1980

In vitro induction of IgM secretion and switching to IgG production in human B leukemic cells with the help of T cells.

In vitro stimulation of the B leukemic cells (B-CLL cells) with normal allogeneic T cells plus PWM induced IgM secretion and a switching from IgM to IgG production. Induction of IgM and IgG production in B-CLL cells with T cells was demonstrated by the presence of the same idiotype in induced Ig as that present in the monoclonal IgM protein in the patient's serum. Both T cells and PWM were required for Ig induction in B-CLL cells, and x-irradiated T cells showed the comparable helper effect. T cells and PWM induced not only Ig secretion but proliferation of B-CLL cells. Cell division was essential for the differentiation of the leukemic cells to Ig-producing cells. PWM-induced, antigen-nonspecific helper factor(s) were also effective in the induction of differentiation of the leukemic cells. Variations existed among T cell donors in the capabilities to induce differentiation of the same leukemic cells, suggesting the requirement of matching of acceptors on B-CLL cells and T effector molecules for the induction of Ig production in B-CLL cells.

Aged↗