Search PubMed⌕ Search

Biomedical subjects

C Morimoto

Publications and source records attributed to C Morimoto.

At least 253 records · Page 14Linked to original sources
PubMed1981

Evidence of aberration of T-cell subsets in aged individuals.

In the present study, T-cell subsets from aged individuals were examined by using anti-BAT (brain-associated thymocyte antigen) serum. Anti-BAT serum was raised against the human fetal brain at 28 weeks of gestation. After absorption wit AB erythrocytes, B-cell lines, and leukaemic cells, anti-BAT serum was T cell-specific but unreactive to normal B cells. The ability of anit-BAT serum-treated lymphocytes from aged individuals to respond to concanavalin A, phytohaemagglutinin, and pokeweed mitogen (PWM) was unaltered even at a high concentration. In PWM-stimulated Ig synthesis, T lymphocytes lacking the anti-BAT serum-reactive T-cell subset enhanced the PWM-stimulated Ig synthesis of autologous B lymphocytes from young individuals. The Con A-induced suppressor function of lymphocytes from aged individuals was not significantly abolished by treatment with anti-BAT serum and complement. In the autologous mixed lymphocyte reaction, the decrease in response was minimal when responder cells from aged individuals was treated with anti-BAT serum even at a high concentration. It is concluded that the T-cell subset with suppressor function is defective in aged individuals.

Adult↗
PubMed1981

Autoantibody to an immunoregulatory inducer population in patients with juvenile rheumatoid arthritis.

The human inducer (T4(+)) and reciprocal cytotoxic/suppressor (T5(+)/T8(+)) subsets have been defined by monoclonal antibodies. In the present study, we examined the relationship of naturally occurring anti-T cell autoantibodies found in patients with active juvenile rheumatoid arthritis (JRA) to these subsets. In one approach, normal T cells were treated with anti-T4 or anti-T8 to eliminate the corresponding subset of cells and then analyzed for reactivity with JRA sera. It was found that JRA sera were reactive with only 15% of an enriched cytotoxic/suppressor population, whereas they reacted with 37% of an enriched inducer population. In reciprocal studies, JRA(+) T cells were eliminated with JRA sera and complement and the residual T cells (JRA(-)) reacted with monoclonal antibodies and indirect immunofluorescence on a fluorescence-activated cell sorter. As expected, the JRA sera and complement treatment of unfractionated T cells markedly diminished the T4(+) subset, whereas there was a concomitant increase in T cells reactive with anti-T5 and anti-T8. A similar diminution in T4(+) T cells was found in the circulating peripheral T cell compartment of patients with active JRA who possessed the JRA antibody. Functional studies demonstrated that removal of the JRA(+) population of T cells diminished phytohemagglutinin and soluble antigen proliferative responses, both of which were previously shown to be functions of T4(+) T cells. More importantly, in the absence of JRA(+) T cells, pokeweed mitogen-stimulated immunoglobulin production was markedly enhanced, despite the concomitant increase in T5(+)/T8(+) cytotoxic/suppressor cells. These results suggest that the JRA serum may define a Qal-like antigen found predominantly on the human inducer population which could activate suppressor and/or other feedback regulatory cells.

Antigens, Surface↗
PubMed1981

Subpopulations of the T4+ inducer T cell subset in man: evidence for an amplifier population preferentially expressing Ia antigen upon activation.

Prior studies demonstrated that Ia molecules were expressed on a fraction of human peripheral T4+ inducer cells upon stimulation by soluble antigen. In the present study, we utilized a fluorescence-activated cell sorter to separate antigen-activated T4+,Ia+ and T4+,Ia- populations and characterized their function. It was found that the T4+,Ia+ population contained the majority of proliferating T cells as assessed by tritiated thymidine incorporation. This proliferation largely appeared to be nonspecific. Despite macrophage repletion, elimination of the Ia+ subset of T cells with monoclonal anti-Ia antibody and complement treatment equally diminished subsequent proliferation to both the triggering antigen and an unrelated antigen. Moreover, the antigen-induced Ia+ subset of T cells alone produced a nonspecific helper factor, LMF. In contrast, the the T4+,Ia- population showed minimal proliferation to soluble antigen and did not generate LMF. Nevertheless, both T4+,Ia+ and T4+,Ia- inducer T cells were required to generate maximal immunoglobulin production by B cells in an antigen-driven system. We conclude that the human T4+ inducer T cell subset is comprised of at least 2 functionally distinct subpopulations, which are capable of acting in a synergistic fashion to provide help to B cells.

Antibodies↗
PubMed1981

Isolation of DNA from DNA/anti-DNA antibody immune complexes in systemic lupus erythematosus.

A low molecular weight DNA fragment was isolated from DNA/anti-DNA antibody immune complexes found in patients with active systemic lupus erythematosus (SLE). Total sera were treated with 40% saturated ammonium sulfate to isolate gamma-globulin fraction and phenolized to partition proteins and nucleic acids. After being treated with RNAase, the sample was labeled at the 5' end with 32P-phosphate and electrophoresed in an 8% polyacrylamide gel, which was dried and autoradiographed. The sample that migrated at positions of molecular weight between 20,000 and 28,000 was susceptible to DNAase I but resistant to S1-nuclease. The data suggest that the immune complexes of SLE patients contain double-stranded DNA with 30 to 40 base pairs.

ABO Blood-Group System↗
PubMed1981

Primary in vitro anti-KLH antibody formation by peripheral blood lymphocytes in man: detection with a radioimmunoassay.

In the present report, a primary in vitro human antibody response to KLH was investigated. Peripheral blood lymphocytes were incubated with antigen for 5 days and then cultured in the absence of KLH for 4 additional days. Maximal anti-KLH antibody production, as measured by radioimmunoassay, occurred at a cell density of 1 X 10(6) and at an antigen concentration of 5 micrograms per culture. The antibody produced was shown to be predominantly of the IgM isotype and specific for KLH antigen in several binding assays. Moreover, no antibody was generated in the absence of T lymphocytes. This in vitro antibody-forming system should be of considerable use in the analysis of the cellular requirements for antibody production and the genetic control of the immune response in man.

Animals↗
PubMed1981

Regulation of in vitro primary anti-DNP antibody production by functional subsets of T lymphocytes in man.

A primary in vitro antibody response to DNP-KLH by peripheral blood lymphocytes in culture was developed. Optimal anti-DNP antibody production, as measured by solid phase radioimmunoassay occurred at a cell density of 1 X 10(6), and an antigen concentration of 5 to 10 micrograms per culture when PBL was incubated with the antigen for 5 days and then cultured in the absence of DNP-KLH for 4 additional days. The antibody produced was shown to be primarily of the IgM isotype and was specific for DNP. In the absence of T lymphocytes, no antibody was generated. The regulatory effects of T4+ and T5+/T8+ subsets on antigen-specific antibody production were determined and it was found that T4+ subset alone provided help for anti-DNP antibody production. In contrast, the T8+ subset did not provide help and more importantly, could suppress anti-DNP antibody production in the presence of T4+ inducer T cells. This in vitro antibody forming system should be of considerable use in the analysis of the cellular requirements for antibody production and genetic control of the immune response in man.

Animals↗
PubMed1980

Regulation of B cell immunoglobulin secretion by functional subsets of T lymphocytes in man.

Two distinct immunoregulatory T cell subsets, termed T4+ and T5+, have been defined in man by monoclonal antibodies. Prior studies have shown that the T4+ T cell population provided help for B cell immunoglobulin (Ig) production and was required for generation of T5+ cytotoxic effector cells. In the present study, the regulatory effects of the T5+ T cell subset on B cell Ig secretion were determined in a pokeweed mitogen-driven system. It was found that the T5+ subset, in contrast to the T4+ subset, was incapable of providing help to B cells and, more importantly, could suppress Ig secretion by B cells in the presence of T4+ inducer T cells, Given earlier studies demonstrating that the T5+ T cell subset suppressed T cell responses as well, this population appears to represent the major suppressor subset in man for T-T and T-B interactions.

Antibodies↗
PubMed1980

Enhancement of lymphocyte response to PHA by lysosomal enzymes from polymorphonuclear leukocytes of RA joint fluid. I. Biological effect on T lymphocyte function.

The effect of polymorphonuclear leukocyte (PMN) granule lysates obtained from joint fluid of RA on the in vitro DNA synthesis of PHA-stimulated autologous lymphocytes from joint fluid was studied. Lymphocytes were cultured for 3 days with or without PMN lysates in 2 ml of RPMI-1640 supplemented with 10% heat-inactivated fetal calf serum (FCS). The lymphocytes were stimulated with phytohemagglutinin (PHA-M). The DNA synthesis was measured by counting the [3H]thymidine incorporation. Lymphocytes from RA joint fluid stimulated with PHA-M showed 19,466+/-987 cpm (mean+/-SE) per 10(6) cells in the absence of PMN lysates. Upon addition PMN lysates to the PHA-stimulated lymphocytes, the maximum in vitro DNA synthesis increased to 44,877+/-1338 cpm. The enhancing effect of PMN lysates was abolished by plasma inhibitors or by passage through a column of protease inhibitor (Trasylol). It was concluded, therefore, that the enhancing effect of PMN lysates on PHA-stimulated lymphocytes may be associated with lysosomal proteases. Based on experiments using separated T and B lymphocytes, the enhancing effect of PMN lysates was considered to result from the activation of T lymphocytes. The results obtained in the present study suggest an important role for lysosomal proteases in the perpetuation of rheumatoid synovitis.

ABO Blood-Group System↗
PubMed1980

Studies of anti-lymphocyte antibody in patients with active SLE. II. Effect of anti-lymphocyte antibody on autoreactive cell clones.

The effect of anti-lymphocyte antibodies of active systemic lupus erythematosus (SLE) on the immune regulation of autoantibody production was studied. The present study demonstrated that there were native DNA (nDNA)-sensitized T lymphocytes even in inactive SLE and no or few nDNA-sensitized T lymphocytes in normal individuals, and that in the inactive stages of SLE suppressor T lymphocytes might inhibit the activation of nDNA-sensitized T lymphocytes eliciting the production of anti-DNA antibodies by B lymphocytes. In the active stage of SLE, the anti-lymphocyte antibodies could eliminate the suppressor function of T lymphocytes or a subset of cells capable of either regulating their appearance or differentiating into them, which inhibited such responses. The different suppression of DNA and extractable nuclear antigen (ENA)-stimulated blastogenic response is further discussed.

Antibodies, Antinuclear↗
PubMed1980

The cellular basis of impaired T lymphocyte functions in the elderly.

Immunologic changes associated with aging were studied by various immunologic tests in 24 aged persons (age range, 76-83) and 25 young persons (age range, 20-40). The responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were depressed in the aged subjects compared to the young ones (p less than 0.05), whereas the responses to pokeweed mitogen (PWM) were similar. The activity of adhereent and non-adherent cells was assessed in various combinations. The adherent cells of aged persons were indistinguishable from those of young persons in their ability to response to Con A. Lymphocytes from the aged synthesized larger in vitro amounts of immunoglobulin than did lymphocytes from the young, when stimulated with PWM. Con A-stimulated T lymphocytes derived from aged subjects showed a variable loss of suppressor activity. The mixed lymphocyte culture reaction with mitomycin-treated allogeneic and autologous cells was also impaired in aged subjects. Such an impaired response in the aged is related to higher incidences of malignant lesions and auto-antibodies.

Adult↗
PubMed1980

Alterations in immunoregulatory T cell subsets in active systemic lupus erythematosus.

To determine whether imbalance among subsets of human T cells exists in patients with systemic lupus erythematosus (SLE), we analyzed peripheral blood lymphocytes in SLE patients during active and inactive stages of disease. For this analysis, we used monoclonal antibodies to the surface antigens of inducer (T4) and suppressor (T5/T8) T cell subsets, as well as a common T cell antigen (T3). In contrast to normal and inactive SLE patients, the percentage of T3+ cells was reduced in all active SLE patients. More importantly, there was a selective decrease in T5+/T8+ suppressor T cells in 12 of 14 active patients, including 1 of 2 patients with drug-induced SLE. Serial analysis of three SLE patients showed a significant correlation between the presence of T5+/T8+ subset and clinical disease activity in all patients. We conclude that aberrations in suppressor T cell subsets are an important correlate of disease in patients with SLE.

Fluorescent Antibody Technique↗
PubMed1980

Characteristic and functional specificity of anti-human BAT (brain associated thymocyte antigen) serum.

A rabbit antiserum to human fetal brain after multiple absorption reacted with 100% of thymocytes, 55% of peripheral blood lymphocytes and 90% of enriched T lymphocytes, but not significantly with B lymphocytes. Spontaneous SRBC rosette formation was inhibited by anti-BAT pretreatment, but EAC-rosette formation remained unaffected. The antiserum was itself highly stimulatory. However, cells treated with the antiserum and complement exhibited marked inhibition of responsiveness to Con A, little effect with PHA and no alteration with PWM. The MLC reaction was inhibited only when the responder cells were treated with the antiserum and complement. Treatment of sensitized lymphocytes with the antiserum and complement caused a dose-dependent suppression of blastogenic response to both PPD and n-DNA. No effect, however, was noted in MIF producing cells. Con A induced suppressor function of lymphocytes was abolished by treatment with the antiserum and complement. These results indicate that the anti-BAT serum obtained by us can be utilized for the isolation of T lymphocyte subsets.

Animals↗
PubMed1979

Studies of anti-lymphocyte antibody of patients with active SLE. I. Cause of loss of suppressor T-lymphocyte function.

Effect of anti-lymphocyte antibody of active systemic lupus erythematosus (SLE) on lymphocyte function was examined. Lymphocytes from normal individuals treated with anti-lymphocyte antibody and complement exhibited marked inhibition of response to concanavalin A (Con A), while the response of lymphocytes to phytohaemagglutinin M (PHA-M) and pokeweed mitogen (PWM) was slightly affected. In mixed lymphocyte culture response, both stimulator and responder cells were insensitive to anti-lymphocyte antibody. Treatment of sensitized lymphocytes with anti-lymphocyte antibody and complement caused a dose-dependent suppression of blastogenic response to purified protein derivatives (PPD). No effect, however, was noted on migration-inhibitory factor (MIF)-producing cells. In PWM-driven Ig synthesis, T lymphocytes lacking the anti-lymphocyte antibody-reactive T-cell subset enhanced PWM-driven Ig synthesis of autologous B lymphocytes. Con-A-induced suppressor function of lymphocytes was abolished by the treatment with anti-lymphocyte antibody and complement. The present study demonstrated that lymphocytes from normal individuals after treatment with anti-lymphocyte antibody and complement showed similar immunological reactivities with lymphocytes from active SLE, indicating that those anti-lymphocyte antibodies could play an important role in defective suppressor cell function.

Antibody-Dependent Cell Cytotoxicity↗