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C Morimoto

Publications and source records attributed to C Morimoto.

At least 235 records · Page 13Linked to original sources
PubMed1983

Hapten-specific carrier-dependent tolerance induction in man in vitro.

We sought to determine whether hapten-specific tolerance can be induced in cultured human lymphocytes in vitro. Unfractionated as well as T and B cells from peripheral blood lymphocytes of healthy human volunteers were cultured with different hapten-carrier conjugates before in vitro challenge with dinitrophenyl (DNP) linked to keyhole limpet hemocyanin. Hapten-specific antibody was detected in the supernatant by solid-phase radioimmunoassay. Both hapten specificity and carrier dependence in addition to the cellular basis of tolerance induction were examined. The results show that hapten-specific tolerance of antibody production was induced by human gamma-globulin (HGG) conjugated to DNP but not by other conjugates of DNP nonhuman gamma-globulin, as well as human serum albumin. Moreover, both T and B cells are involved in tolerance induction to DNP-HGG in vitro. The significance of tolerance in human in vitro for the specific therapy of autoimmune disease is discussed.

Antigens↗
PubMed1983

Ultrastructural localization of alkaline phosphatase in the calcifying epithelial odontogenic tumor.

The localization of alkaline phosphatase in a calcifying epithelial odontogenic tumor obtained from a 53-year-old man was examined cytochemically. The majority of enzyme activity was associated with the epithelial cell membranes of the tumor, and faint activity was found in the cell membranes facing the adjacent stromal tissue. The reaction product of ALP was also detected in some membrane-bound vacuoles (lysosomes) and the Golgi apparatus of tumor cells. It is suggested that the appearance of enzyme activity associated mostly with the epithelial cell membrane may be related to transport function of cell membranes.

Alkaline Phosphatase↗
PubMed1983

Functional differences of anti-T-cell antibody in patients with systemic lupus erythematosus and ulcerative colitis.

The loss of suppressor T-cell function results in an abundant production of autoantibodies in systemic lupus erythematosus (SLE). As a cause of this suppressor T-cell defect, anti-T-cell antibody seems to be of prime importance. On the other hand, anti-T-cell antibodies can be detected in various other autoimmune diseases, but their functional characteristics have not been determined. In the present study, the functional characteristics of anti-T-cell antibody from a selected subgroup of patients with ulcerative colitis (UC) were compared with those from patients with SLE. Anti-T-cell antibody from the patients with SLE reacted with a T8 subset, resulting in a suppressor defect, whereas anti-T-cell antibody from the UC patients reacted primarily with a T4 subset. Functionally, SLE- T cells failed to proliferate in response to concanavalin A, whereas UC- T cells from UC patients failed to proliferate in response to phytohaemagglutinin. In the Ig synthesis system, both SLE- and UC- T cells increased Ig production of B cells. Since UC+ T cells did not contribute to the generation of Con-A-inducible suppressor activity, we believe that serum from the selected subgroup of patients with UC reacted with the inducer T-cell subset.

Adult↗
PubMed1983

In vitro nucleoside specific immune response by lymphocytes from systemic lupus erythematosus.

The in vitro immune response of systemic lupus erythematosus (SLE) lymphocytes to nucleosides conjugated to keyhole limpet hemocyanin (KLH) (A,G,C,T-KLH) was investigated. The nucleosides were chosen not only because they are a part of nucleic acid antigen and involved in autoimmunity, but also because nucleoside covalently bound to either soluble IgG or cells had been shown to induce unresponsiveness in mice. A significant proliferation index was induced in SLE lymphocytes, as compared with normal or rheumatoid arthritis (RA) lymphocytes in vitro [in (A,G,C,T)-KLH, 1 microgram/ml; stimulation index = M +/- SE, SLE 2.10 +/- 0.26, RA 1.06 +/- 0.14, normal 1.12 +/- 0.12 P less than 0.05]. Lymphocytes from SLE patients responded specifically to low doses of (A,G,C,T)-KLH and not to the protein carrier KLH alone. A solid-phase radioimmunoassay was developed to detect nucleoside-specific antibody. SLE lymphocytes spontaneously produced high levels of anti-A,G,C,T antibody. This was further increased by antigenic stimulation, but not with pokeweed mitogen (PWM) stimulation. In contrast normal lymphocytes failed to produce anti-A,G,C,T antibody either spontaneously or in response to antigen. However, normal lymphocytes produced antibody after stimulation with PWM. More importantly, anti-A,G,C,T antibody production by SLE lymphocytes was suppressed by preincubation with A,G,C,T-IgG (A,G,C,T-HGG). The antigen-specific unresponsiveness caused by A,G,C,T-HGG was demonstrated by the observation that preincubation with A,G,C,T-HGG did not affect the production of anti-dinitrophenyl antibody response. The ability to manipulate the altered response of SLE lymphocytes to nucleic acid antigens may have therapeutic implications in these patients.

Adenosine↗
PubMed1983

Generation of antigen-specific suppressor cells in vitro in man.

The generation of human antigen-specific suppressor cells in vitro was examined in a primary anti-DNP antibody-forming system. It was found that specific T8 suppressor cells could be induced in vitro with high doses of antigen. The suppression obtained was macrophage dependent and carrier specific. KLH-specific T8 suppressor cells suppressed the anti-DNP antibody response induced by DNP-KLH but not by DNP-FGG. Similarly, T8 suppressor cells induced with FGG specifically suppress the anti-DNP response stimulated by DNP-FGG. These T8+ suppressor cells bear Ia molecules arising as a consequence of activation. This in vitro antigen-specific system should be useful for the further dissection of human immunoregulatory circuits.

Animals↗
PubMed1983

Selective inhibition of anti-nucleoside-specific antibody production by nucleoside-ricin A conjugate.

The effect of the preincubation of peripheral blood lymphocytes, from SLE patients, with nucleoside-ricin A conjugates on spontaneous A,G,C,T antibody production was examined. Enhanced spontaneous anti-nucleoside-specific antibody (anti-A,G,C,T antibody) production by SLE B cells was selectively inhibited by pretreatment in vitro with nucleosides conjugated to the ricin A chain. The selective suppression was demonstrated by the lack of suppression of the anti-DNP response or of polyclonal IgG production by pretreatment that did suppress anti-A,G,C,T production by the lymphocytes of eight patients with SLE. Furthermore, pretreatment of B cells, but not of T cells, with nucleoside-ricin A conjugates inhibited the A,G,C,T antibody response by these B cells. Thus, (A,G,C,T)-BGG-ricin A conjugates bind directly to the nucleoside-specific B cells via their antigen receptors. This demonstration of the selective elimination of B cells might have therapeutic applications in SLE.

Antibodies, Antinuclear↗
PubMed1983

Direct demonstration of the human suppressor inducer subset by anti-T cell antibodies.

Prior studies indicated that sera of patients with active juvenile rheumatoid arthritis (JRA) contain anti-T cell antibodies reactive with the T4+ inducer population. More important, depletion of this T cell subset with JRA anti-T cell antibodies (JRA+ T cells) and C abrogated T5/T8+ suppressor T cell function. In the present study, we utilized Ig-coated plate techniques and JRA anti-T cell antibodies to fractionate the T4+ population into T4+JRA+ and T4+JRA- subsets and characterize the individual T4+ inducer subset. It was shown that whereas only the T4+JRA- population responded maximally to the soluble antigens, TT and mumps, both T4+JRA+ and T4+JRA- subsets proliferated equally well to mitogens and alloantigens. Furthermore, B cell immunoglobulin production induced by T4+JRA- T cells was approximately twice that induced by the reciprocal T4+JRA+ subset. In contrast, the T4+JRA+ subset alone activated T8+ T cells to become suppressor effector cells. These results suggest that the T4+JRA+ subset is the inducer of suppressor subpopulation whereas the T4+JRA- subset functions maximally as the inducer of B cells. It is believed that the suppressor inducer population may have a central role in the immunoregulatory network in man.

Antibody Formation↗
PubMed1983

Immunoregulatory human T lymphocytes triggered as a consequence of viral infection: clonal analysis of helper, suppressor inducer and suppressor effector cell populations.

The regulatory functions of a series of human T cell clones specific for an autologous Epstein-Barr virus transformed B lymphoblastoid cell line were examined. Two T4+ T cell clones, termed AT4II and AT4IV, and one T8+ clone, AT8III, were maintained in culture for greater than or equal to 9 months and were characterized in detail. Both T4+ clones provided helper function for autologous B cell immunoglobulin production when added to unstimulated peripheral blood mononuclear cells. In addition, these same clones produced soluble inducer factors after specific antigenic stimulation. However, when AT4II, AT4IV and their subclones were tested on pokeweed mitogen stimulated peripheral blood mononuclear cells, it was found that AT4IV provided help for immunoglobulin production whereas AT4II cells were strongly suppressive. This suppression by AT4II was indirect and required the presence of fresh, autologous, unirradiated T8+ cells. In contrast, the T8+ AT8III clone markedly inhibited Ig production by autologous B cells in the absence of any additional T8+ cells from peripheral blood and produced a soluble suppressor factor upon specific antigenic triggering. Thus, after stimulation with autologous Epstein-Barr virus transformed cells, at least three discrete regulatory human T cell populations can be defined at the clonal level: helper, inducer of suppression and suppressor effector clones.

Antibody-Producing Cells↗
PubMed1983

Accumulation of guanine-cytosine-enriched low M.W. DNA fragments in lymphocytes of patients with systemic lupus erythematosus.

The fate of the newly synthesized DNA in peripheral blood lymphocytes from patients with systemic lupus erythematosus was examined. After lymphocytes were stimulated with the mitogen phytohemagglutinin (PHA), DNA was pulse-labeled with radioactive thymidine and was analyzed by sucrose density gradient centrifugation. Two classes of DNA were identified; the main DNA fraction that migrated to the same position as that of control samples, and low m.w. DNA fragments. The low m.w. DNA fragments were further characterized: i) The amount of low m.w. fragments increased with increasing time of culture after PHA stimulation. ii) The guanine cytosine content was 47% of the total bases at 4 days after PHA stimulation. iii) The base composition was similar to that of DNA fragments isolated from DNA/anti-DNA antibody immune complexes. These results lead us to propose that guanine cytosine-enriched low m.w. DNA fragments accumulate in cells after nuclear DNA is degraded, and that these fragments may serve as a primary source of autoantigen for anti-DNA antibody production. In addition, they may interfere with normal cellular metabolism.

Base Sequence↗
PubMed1982

In vitro immune response of SLE lymphocytes. The mechanism involved in B-cell activation.

Peripheral blood lymphocytes from 26 patients with systemic lupus erythematosus (SLE) and six normal individuals were tested for IgG synthesis in the presence or absence of PWM. Lymphocytes from patients with active SLE synthesized increased amounts of IgG in the absence of PWM and reduced amounts of IgG in the presence of PWM. Serum from patients with active SLE had an enhancing effect on the in vitro IgG synthesis of normal lymphocytes. The IgG or F(ab')2 fractions of SLE serum retained the enhancing effect on in vitro IgG synthesis, and the enhancing activity was absorbed by human spleen cells. As little as 4 h of incubation with SLE serum was needed for the enhancing activity of normal lymphocytes. Treatment of B lymphocytes appeared to be of main importance for an increase in the in vitro IgG synthesis of SLE serum-treated lymphocytes. These results suggest that anti-B-lymphocyte antibodies from patients with active SLE are responsible in part for the hyperactive response of SLE B lymphocytes.

Antibody-Producing Cells↗
PubMed1982

Heterogeneity of human T4+ inducer T cells defined by a monoclonal antibody that delineates two functional subpopulations.

A monoclonal antibody termed anti-T4 that detected approximately 60% of peripheral blood T lymphocytes was shown to define the human inducer population. In the present study, we characterized three additional monoclonal antibodies, anti-T4A, anti-T4B, and anti-TQ1, that were reactive with a similar percentage of T lymphocytes. Anti-T4A, anti-T4B, and anti-T4 delineated identical cell populations, while those defined by anti-TQ1 differed in several respects: 1) Anti-TQ1 stained a minority (less than 7%) of thymocytes, whereas the other antibodies stained a majority (80%); 2) Anti-TQ1 reacted with 70 to 85% of T4+ lymphocytes, but also stained 50% of T cells within the T4- (T8+) cytotoxic/suppressor subset; 3) The antigen defined by anti-TQ1 was not restricted in its expression to T cells; it defined a fraction of normal B and null lymphocytes as well as non-T cell lines. In vitro studies indicated that the subpopulations of T4+ T lymphocytes delineated by anti-TQ1 were functionally distinct. Although T4+TQ1+ and T4+TQ1- T cells proliferated in an equal fashion to soluble antigen and alloantigen, only the T4+TQ1+ subset was responsible for maximal proliferation in autologous MLR. This T4+TQ1+ subset contained a population of lymphocytes reactive with the previously defined JRA autoantibody. In contrast, the T4+TQ1-, but not the T4+TQ1+, subset provided the majority of T cell help for B cell immunoglobulin production in a pokeweed-driven system. We conclude that the subpopulation of T4+ inducer cells responsible for maximal helper activity in T-B interactions is restricted to a minor subpopulation of T4+ lymphocytes.

Adolescent↗
PubMed1982

Communicative interactions between subpopulations of human T lymphocytes required for generation of suppressor effector function in a primary antibody response.

The cellular interactions necessary for generation of human T suppressor effector function were examined in a primary in vitro antigen-specific anti-DNP antibody-forming system. During the induction of the anti-DNP response, it was found that T cells of both T4+ and T8+ subsets were necessary to suppress antibody formation, whereas after activation, only the T8+ subset was required. Thus, a population of T4+ T cells appears to be necessary to activate or induce a subset of T8+ cells to suppress. The T4+ suppressor inducer population, like the resting or activated T8+ suppressor effector subset, was sensitive to low dose irradiation. Moreover, the radiosensitive T4+ subset and the previously defined T4+JRA+ subset were shown to be functionally similar or complementary in that both were required for generation of suppressor effector function. These findings suggest that T-T interactions between radiosensitive T4+JRA+ T cells and radiosensitive T8+ T cells are necessary for suppression of primary antigen-specific antibody production in man.

Antibody Formation↗
PubMed1982

Dna isolated from DNA/anti-DNA antibody immune complexes in systemic lupus erythematosus is rich in guanine-cytosine content.

DNA fragments were isolated from DNA/anti-DNA antibody immune complexes of systemic lupus erythematosus. Hybridization experiments indicated that DNA isolated from immune complexes originates from human nuclear DNA. Two classes of DNA were identified by polyacrylamide gel electrophoresis. The m.w. of small fragments was 25,000 with 30 to 40 base pairs, and that of large fragments was 100,000 with 150 base pairs. The average guanine-cytosine (G-C) content in the small fragments was 55% of total bases, and that in the large fragments was 45%. Compared with the average 38% G-C content of total human DNA, the antigen DNA is rich in G-C content. Such unusually high G-C content can alter DNA structure, which may serve as the target for antibody production.

Antigen-Antibody Complex↗
PubMed1982

Correlation between clinical activity of systemic lupus erythematosus and the amounts of DNA in DNA/anti-DNA antibody immune complexes.

The relationship between clinical activity of systemic lupus erythematosus (SLE) and molecular sizes of DNA fragments isolated from DNA/anti-DNA antibody immune complexes were examined. Among sera from twenty-eight patients with SLE examined, three different molecular sizes of DNA were identified, namely, DNA of m.v. 25,000 with 30 to 50 base pairs (bp); m.w. 100,000 with 150 to 200 bp; and m.w. 200,000 with 300 bp. On the basis of the molecular sizes of DNA fragments, we can divide patients with SLE into four groups. The first group contained DNA predominantly of m.w. 25,000. The second group contained DNA predominantly of m.w. 100,000. The third group contained DNA of m.w. 200,000. The fourth group contained both m.w. 25,000 and 100,000. A method to quantitate the amounts of DNA in DNA/anti-DNA immune complexes was developed. The amount of DNA fragments was estimated by measuring the amount of 32P-phosphate incorporated into 5 ends of DNA. Patients with severe disease tended to have greater amounts of DNA (up to 400 ng/ml serum). Two serial studies also support this result. Thus, the quantitative analysis shows that the amount of DNA in the immune complexes is highly correlated with disease activity (r = 0.864; p less than 0.001). These results suggest that DNA/anti-DNA immune complexes may play some role in the pathogenesis of lupus nephritis.

Adolescent↗
PubMed1981

Immunodeficiency associated with loss of T4+ inducer T-cell function.

We investigated the immune function of a patient with anergy and acquired hypogammaglobulinemia. Despite normal numbers of B cells and T4+ inducer and T5+ suppressor T cells, this patient's lymphocytes did not produce immunoglobulin, proliferate in response to soluble antigens, or generate helper factors in vitro. In addition, her T4+ T cells did not express la molecules after stimulation by soluble antigen. In mixing experiments, her T cells did not induce immunoglobulin secretion by B cells from a normal, HLA-D-identical sibling; this failure was not due to excessive suppression, since the patient's T cells did not abrogate immunoglobulin production by the normal sibling's T and B cells. Moreover, the patient's B cells secreted immunoglobulin in the presence of the sibling's T4+ cells. In contrast to the deficient inducer cells, the patient's T5+ T cells were capable of expressing suppressor-cell functions. These results indicate that immunodeficiency may occur because of a selective loss of T4+ inducer function.

Agammaglobulinemia↗