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C Morimoto

Publications and source records attributed to C Morimoto.

At least 217 records · Page 12Linked to original sources
PubMed1987

The 2H4 molecule but not the T3-receptor complex is involved in suppressor inducer signals in the AMLR system.

It is suggested that autologous mixed lymphocyte reaction (AMLR) may play an important role in generating suppressor inducer signals and in down-regulating the immune response following self-major histocompatibility recognition. In the present study, monoclonal antibodies directed at cell surface structures on T4+ cells activated in AMLR were used to define the molecules important in the generation of the suppressor inducer signal. The density of a 200/220-kDa structure, termed 2H4, increased on T4 cells during activation in AMLR and furthermore a strong correlation was observed between the generated suppressor inducer activity of such cells and the density of the 2H4 antigen. More importantly, we showed that treatment of AMLR activated T4 cells with anti-2H4 but not anti-T3 or T4 antibody abolished the suppressor inducer function of these cells. These results suggest that the 2H4 molecule but not the T3-receptor complex plays an important role in generating suppressor inducer signals in the AMLR system.

Antibodies, Monoclonal↗
PubMed1987

A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody.

The cell surface phenotype of peripheral blood lymphocytes (PBL) of systemic lupus erythematosus (SLE) patients was characterized with the anti-2H4 monoclonal antibody that defines the human suppressor inducer subset. The T4+2H4+ population of cells has been shown to be critical for the activation of T8+ suppressor cells. Patients with SLE has a markedly decreased percentage of T4+2H4+ cells (13 +/- 2%) in their PBL compared with normal controls (21 +/- 1%) (P less than 0.001). This reduction was greatest in patients with active SLE, especially those with renal disease. Serial analysis of patients with SLE and renal disease showed a correlation between percent positive circulating T4+2H4+ cells and disease activity. Moreover, there was a significant correlation between a low percentage of T4+2H4+ cells and decreased suppressor-inducer function in autologous mixed lymphocyte reaction-activated T4+ cells from SLE patients. Thus, a deficiency exists in SLE patients with active renal disease in the T4+2H4+ suppressor-inducer T cell subset.

Adolescent↗
PubMed1986

The role of the 2H4 molecule in the generation of suppressor function in Con A-activated T cells.

The molecular basis for the suppression generated in a concanavalin A (Con A)-activated T cell culture remains unknown. In this study, we have attempted to determine whether the 2H4 and 4B4 molecules on Con A-activated T cells play some role in the generation of suppression by such cells. We have shown that Con A-activated suppressor cells belong to the 2H4+ subset of T cells but not the 4B4+ (2H4-) subset. Con A-activated T cells exerted their optimal suppressor function on day 2 in culture, a time at which the expression of 2H4 on such cells was maximal and 4B4 was minimal. Furthermore, the stimulation of T cells with the higher concentration of Con A generated the stronger suppressor function. At the same time, both 2H4 expression and density were increased and 4B4 expression and density were decreased on such Con A-activated T cells. More importantly, the treatment of Con A-activated T cells with anti-2H4 antibody but not with anti-4B4, anti-TQ1, or anti-T4 antibodies can block the suppressor function of such cells. Taken together, the above results strongly suggest that the 2H4 molecule itself may be involved in the generation of suppressor function in Con A-activated T cells. The 2H4 antigen on such cells was shown to be comprised of 220,000 and 200,000 m.w. glycoproteins. Thus this study indicates that the 220,000 and 200,000 m.w. structure of the 2H4 molecule may itself play a crucial role in the generation of suppressor signals of Con A-activated cells.

Antibodies, Monoclonal↗
PubMed1986

DNA-daunorubicin complexes specifically suppress in vitro spontaneous anti-DNA antibody production in lymphocytes of patients with systemic lupus erythematosus.

Elevated production of anti-DNA antibody in patients with systemic lupus erythematosus (SLE) is a central problem in the pathogenesis of tissue injury. In the present study, we attempted to manipulate anti-DNA antibody production through the antigen-cytotoxic drug conjugates, DNA-daunorubicin complexes. The effect of DNA-daunorubicin complexes was determined by examining SLE lymphocytes for spontaneous in vitro production of anti-DNA antibody. These complexes, at 2 micrograms/ml, suppressed anti-DNA antibody production, but not total IgG production, which suggests that specific suppression of anti-DNA antibody production was achieved at this concentration. We believe that the DNA-daunorubicin complexes affected mainly B cells, since such suppression was obtained by treating B cells, as well as B plus T cells. Furthermore, the complexes had no effect on the proliferative responses of SLE T cells to DNA, phytohemagglutinin, or concanavalin A. These results indicate that DNA-daunorubicin complexes may have the potential for selectively suppressing anti-DNA antibody production in patients with SLE.

Antibodies, Antinuclear↗
PubMed1986

The cellular basis for the induction of antigen-specific T8 suppressor cells.

The cellular basis for the generation of antigen-specific T8 suppressor cells with high doses of antigen has been studied. We separated the T4 subset of human T cells into T4+2H4+ and T4+2H4- subpopulations with a recently developed monoclonal anti-2H4 antibody. T8 cells could be consistently activated to suppress a primary anti-2,4-dinitrophenyl (DNP) antibody response in vitro with unfractionated T4 cells or with the T4+2H4+ subset but not the T4+2H4- subset. In contrast, the T4+2H4- subset functioned as the helper inducer for the anti-DNP antibody response. With keyhole limpet hemocyanin (KLH)-stimulated T4+2H4+ cells we could efficiently induce antigen-specific suppressor activity of fresh T8 cells. In contrast, the T4+2H4+ subset could not effect suppression in the absence of T8 cells. Our findings indicate that the T4+2H4+ subset of human T cells is the suppressor inducer of specific T8 cells in an antigen-specific DNP-KLH system.

Antibodies, Monoclonal↗
PubMed1985

Definition of the T-lymphocyte inducer of suppression in primates using a monoclonal antibody.

Since some of the conserved antigens between man and phylogenetically lower primate species may be more immunodominant on lymphocytes of the lower primate species, we reasoned that immunization of mice with lymphocytes from lower primates might prove a useful strategy for developing monoclonal antibodies which recognize functionally important structures on both human and nonhuman primate lymphocytes. In employing this approach for the development of monoclonal antibodies, we have developed the antibody anti-2H4 which recognizes a structure on both T on non-T mononuclear cells of a wide array of primate species. 2H4+ rhesus monkey T lymphocytes exhibited a greater proliferative response to lectin and alloantigenic stimulation than 2H4- cells, suggesting that anti-2H4 might separate primate T lymphocytes into functionally distinct cell populations. In fact, helper activity for antibody production by rhesus monkey B lymphocytes in response to pokeweed mitogen (PWM) resided in the 2H4- T-cell population. Furthermore, the 2H4+ T-lymphocyte population activated the suppressor function of T8+ rhesus monkey cells. The fact that the surface antigen which defines this T-cell subset is widely conserved in nonhuman primates suggests that anti-2H4 recognizes a functionally important structure.

Animals↗
PubMed1985

Systemic lupus erythematosus: delineation of subpopulations by clinical, serologic, and T cell subset analysis.

Patients with systemic lupus erythematosus (SLE) (n = 194) were analyzed for correlation of clinical features. In addition, the proportions of the two major T cell subsets were determined in 87 subjects. Two patient subgroups were discerned: one in which severe renal disease, leukopenia, and thrombocytopenia predominated, and a second in which sicca syndrome and involvement of the central nervous system, lungs and muscle occurred. The ratio of T helper/inducer to T suppressor/cytotoxic cells was reduced in the first group and increased in the second. We conclude that SLE does not comprise a single disease entity, but rather represents a number of syndromes with overlapping clinical features. The correlation of clinical symptoms with the proportions of circulating T cell subsets suggests that several immunologic mechanisms may underlie the various types of SLE.

Adult↗
PubMed1985

Functional and phenotypic studies of Japanese adult T cell leukemia cells.

The cell surface marker profile and functional analysis of peripheral blood lymphocytes from 11 Japanese adult T cell leukemia patients were studied. The phenotypic analysis of Japanese adult T cell leukemia (ATL) cells by a series of 13 monoclonal antibodies showed that all ATL cells are anti-T4 reactive but some differ in their expression of T3, T11, and T12 antigens. Thus, considerable phenotypic heterogeneity exists in these populations of leukemia cells. When analyzed in functional assays, ATL cells were suppressive when added to a pokeweed mitogen- (PWM) driven Ig synthesis system. However, the suppression mechanism seemed to be more complex than originally conceived. ATL cells examined in this study seem to function mainly as an inducer of suppressor cells, and as such, activate normal T8 precursors of suppressor cells rather than function as suppressor effector cells. In addition, no evidence was obtained to suggest that suppression of PWM-stimulated IgG synthesis was mediated by natural killer (NK) activity of ATL cells. Rather, ATL cells seem to be markedly deficient in NK activity. These studies suggest that the majority of ATL cells tested are representative of and seem to be the leukemic counterparts of the T4+ suppressor inducer subset.

Adult↗
PubMed1985

The isolation and characterization of the human suppressor inducer T cell subset.

Immunization of mice with lower primate lymphoid cells has provided a useful strategy for raising monoclonal antibodies against functionally important surface determinants on human T lymphocytes. We have developed a monoclonal antibody, anti-2H4, which defines functionally unique human T cell subsets. This anti-2H4 antibody was reactive with approximately 42% of unfractionated T cells, 41% of T4+ inducer cells, and was reactive with approximately 54% of T8+ cytotoxic/suppressor population. Anti-2H4 was not reactive with human thymocytes, but reacted with subsets of peripheral blood B cells and null cells. This antibody subdivided peripheral blood T4+ cells into two functionally distinct populations. The T4+2H4+ subset proliferate well to concanavalin A (Con A) stimulation, but poorly to soluble antigen stimulation, and provides poor help to B cells for PWM-induced Ig synthesis. The T4+2H4- subset, in contrast, proliferates poorly upon stimulation with Con A, but well on exposure to soluble antigen, and provides a good helper signal for PWM-induced Ig synthesis. What is, perhaps, most important, the T4+2H4+ subset functions as the inducer of the T8+ suppressor cells. Previous attempts to define the latter subset of cells has relied heavily on the use of specific autoantibodies present in the sera of patients with juvenile rheumatoid arthritis (JRA) and systemic lupus erythematosus (SLE). The present results suggest that anti-2H4 antibody defines the human suppressor induced subset of lymphocyte previously described as T4+JRA+. Last, the results reemphasize the previously documented remarkable structural conservation of certain T cell-specific determinants on lymphocytes of phylogenetically distant primates.

Animals↗
PubMed1985

The isolation and characterization of the human helper inducer T cell subset.

Monoclonal antibody anti-4B4 was produced by fusing NS1 myeloma with spleen cells of a mouse immunized with Saguinus oedipus lymphocyte. This anti-4B4 antibody defines a 135-KD cell surface protein that is widely distributed throughout the hematopoietic system. More importantly, anti-4B4 is reactive with functionally unique human T cell subsets. Anti-4B4 antibody was reactive with approximately 41% of unfractionated T cells, 41% of T4+ inducer cells, and approximately 43% of T8+ cytotoxic/suppressor population. This antibody subdivided peripheral blood T4+ cells into two functionally distinct populations. The T4+4B4+ subset proliferates relatively poorly upon stimulation with Con A and autologous cell antigens (AMLR) but well on exposure to soluble antigens, and it provides a good helper signal for PWM-induced Ig synthesis. The T4+4B4- subset, in contrast, proliferates well to Con A stimulation and autologous cell antigen (AMLR) but relatively poorly to soluble antigen stimulation, and provides little help to B cells for PWM-induced Ig synthesis. The T4+4B4- subset is largely 2H4+ and functions as the inducer of the T8+ suppressor cells. Thus, the present results suggest that one can divide the human T4 population into two major subsets that are phenotypically and functionally distinct, the human helper inducer subset (T4+4B4+/H.I.) and its reciprocal population defined by anti-2H4, the suppressor inducer subset (T4+2H4+/S.I.).

Animals↗
PubMed1984

Cellular interaction between subsets of T8 population for maximal suppression of antigen-specific antibody response.

The characterization of human keyhole limpet hemocyanin (KLH)-specific T8 suppressor cell (T8 KLH) generated in vitro with high doses of antigen by using peripheral blood lymphocytes is described. The cellular basis for the generation of specific suppressor-effector functions was examined and it was shown that radioresistant T8 KLH cells could induce a second set of radiosensitive suppressor-effector cells found in a freshly isolated T8 population. Moreover, the T8 KLH population could be divided into T8 KLH TQ1+ and T8 KLH TQ1- subsets. Both subsets were required for maximal suppression of the anti-DNP antibody response, since neither subset alone induced more than minimal suppression. These results demonstrated that several functionally distinct T8 subpopulations of cells exist, and it is suggested that further resolution of these complex immunological networks in man will be facilitated by the development of unique reagents capable of defining the heterogeneity of the cells involved in suppressor functions.

Antibodies, Monoclonal↗
PubMed1984

Suppressor T cell function in patients with rheumatoid arthritis complicated by vasculitis.

Concanavalin A (Con A)-induced suppressor T cell activity was determined in 10 rheumatoid arthritis (RA) patients with vasculitis, 34 RA patients without vasculitis, and 10 healthy individuals. The percent Con A-induced suppression in RA patients with vasculitis was 24.6. In contrast, it was 68.4% in those RA patients without vascular lesions. Further, the proportion of T cells reactive with OKT8 monoclonal antibody was also decreased in RA patients with vasculitis. Accordingly, the reduced Con A-induced suppressor T cell activity in these RA patients resulted, in part, from the reduction in the number of cells of the suppressor T cell subset. Those patients with vascular lesions also had a higher percentage of positive antilymphocytotoxic antibodies than RA patients without vasculitis. Since the differences in Con A-induced suppressor T cell activity and frequency of positive antilymphocytotoxic antibodies were so great, we believe RA patients with vasculitis could be recognized as a disease group distinct from RA patients without vasculitis.

Adult↗
PubMed1984

Cellular mechanism of DNA-specific antibody synthesis by lymphocytes from systemic lupus erythematosus patients.

The cellular mechanism of anti-DNA antibody synthesis in patients with systemic lupus erythematosus (SLE) was studied by DNA-specific solid-phase radioimmunoassay. Anti-DNA antibody synthesis in response to DNA was T-dependent, and the experiments with reconstituted lymphocytes from identical twins discordant for SLE showed that B cells and T cells from SLE patients must cooperate to synthesize anti-DNA antibody. Anti-DNA antibody synthesis by lymphocytes from patients with inactive SLE was enhanced by T4 cells and suppressed by T8 cells in response to DNA. Although T4 cells from patients with active SLE could enhance anti-DNA antibody synthesis by autologous B cells, their T8 cells could not suppress anti-DNA antibody synthesis by autologous B cells. These results indicate that elevated anti-DNA antibody synthesis in response to DNA in patients with active SLE is due to abnormalities of both SLE B cells and SLE T cells. They further indicate that dysfunction of T8 cells from patients with active SLE may, in part, be responsible for deficient regulation of anti-DNA antibody synthesis.

Antibodies↗
PubMed1984

Reactivity of inducer cell subsets and T8-cell activation during the human autologous mixed lymphocyte reaction.

To characterize the responding T cells in the autologous mixed lymphocyte reaction (AMLR), T cells were fractionated into purified subpopulations employing monoclonal antibodies and a variety of separation techniques including fluorescence-activated cell sorting. It was found that isolated T4 cells, but not T8 cells, proliferated in response to autologous non-T cells. More importantly, within the T4 subset, the autoreactive population was greatly enriched in a fraction reactive with an autoantibody from patients with juvenile chronic arthritis (JRA) or the monoclonal antibody anti-TQ1. Although T8 cells themselves were unable to proliferate in the AMLR, they could be induced to respond in the presence of either T4 cells or exogenous IL-2 containing medium. This was demonstrated by direct measurement of tritiated thymidine uptake by T8 cells during the course of the AMLR as well as by analysis of their relative DNA content. Taken together, these data indicate that the AMLR represents a complex pattern of immune responsiveness distinct from that observed in response to soluble antigen or alloantigen. The precise function of this T-cell circuit remains to be determined.

Adult↗
PubMed1984

Relationship between systemic lupus erythematosus T cell subsets, anti-T cell antibodies, and T cell functions.

Previous studies have shown that patients with systemic lupus erythematosus (SLE) had differing T cell T4+/T8+ ratios and that the ratio correlated with clinical features of the disease. In the present study, we wished to determine whether the peripheral blood T cell subsets in these patients were related to the specificity of anti-T cell antibodies found in their plasma. Plasma from 24 SLE patients that reacted with greater than 20% of normal T cells were analyzed for their effect on in vitro pokeweed mitogen-stimulated immunoglobulin synthesis and for their reactivity with human T4+ and T8+ cells. Anti-T cell antibodies found in SLE patients have a spectrum of reactivities. We concentrated upon antibodies that interfere with suppressor function. One group of SLE anti-T cell antibodies reacts preferentially with the T8+ suppressor effector cell whereas another is reactive with T4+ suppressor inducer subsets. SLE patients with high T4+/T8+ ratios had anti-T cell antibodies predominantly reactive with the T8+ suppressor effector cells. Patients with low T4+/T8+ ratios, on the other hand, had anti-T cell antibodies reactive with either the T4+ suppressor inducer or with both the T4+ suppressor inducer and T8+ suppressor effector cells. In addition, a fourth group was defined whose anti-T cell antibodies were neither reactive with a functional T4+ suppressor inducer nor a functional T8+ suppressor effector cells. There was a significant correlation between the circulating T4+/T8+ ratio of peripheral T cells in these patients and the relative ability of their anti-T cell antibodies to kill T8+ cells vs. T4+ cells (gamma = 0.666, P less than 0.001). These results support the notion that in SLE different cellular defects in the immunoregulatory circuit underlie the development of autoimmune reactions and that the anti-T cell antibodies may cause numerical and functional deficiencies in T cell subsets.

Antibodies↗
PubMed1984

Anti-T cell antibody in juvenile rheumatoid arthritis.

One hundred-and-seven patients with juvenile rheumatoid arthritis (JRA) were studied for the presence or absence of an autoantibody in their sera directed against T cells. Using an indirect immunofluorescence technique on a fluorescence activated cell sorter, 71% of all patients were found to be positive on at least one sample. When studied according to the mode of onset of disease 75% of those with systemic onset, 70% with a pauciarticular, and 68% of those with a polyarticular onset were positive. Longitudinal studies appeared to suggest a correlation with disease activity, particularly in individual patients who were positive, while remission was almost invariably associated with negative testing for anti-T cell antibodies. These findings suggest that the anti-T cell antibody may be a useful diagnostic test in JRA and of benefit in monitoring disease activity and remission of disease.

Adolescent↗