Biomedical subjects
Publications and source records attributed to T Sakane.
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Autoantibodies including rheumatoid factor (RF), anti-DNA antibody (ADA), and anti-nuclear factor (ANF) in addition to cold agglutinin and heterophil antibody titers were tested for in a total of 219 patients with common viral diseases. The diseases included varicella, influenza, measles, mumps, herpes zoster, hand-foot-mouth syndrome, and exanthem subitum . A high incidence of RF (23%) was demonstrated in varicella patients, and ADA and ANF (16% and 12%, respectively) were most frequently detected in the influenza cases. Those autoantibodies were most frequently found in patients with influenza. Each serum complement component and total hemolytic complement (CH50) were also assayed. Elevated levels of the fourth (C4) and ninth (C9) components of complement, along with elevated CH50, were observed in most patients. Follow-up studies indicated that those autoantibodies as well as other antibodies disappeared 3 to 8 weeks after the onset of infection. The present study indicates that substantial but transient alterations in the immune system accompanied by autoimmune phenomena and elevated levels in the complement components can occur in viral infections.
Neutrophils from the synovial fluid (SFN) of 10 patients with active rheumatoid arthritis (RA) were investigated to determine the generation of oxygen intermediates (OI) (O2-, H2O2, OH .), chemiluminescence, and lysosomal enzymes (lysozyme and beta-glucuronidase). Lymphocytes from healthy individuals were cocultured at 37 degrees C for 17 hr with SFN from the patients and the number of OKT4+, OKT8+, and OKT3+ cells and the response to mitogens were determined. A markedly increased OI and slightly elevated lysosomal enzyme levels were observed in SFN from patients. Coculture of lymphocytes with SFN resulted in a decreased number of OKT4+ and OKT8+ cells and a greatly reduced response to Con A and mildly diminished response to PHA, while OKT3+ cells were not affected. The simultaneous addition of superoxide dismutase and catalase restored the impairment of monoclonal antibody reaction and lymphocyte responsiveness almost to control levels. It is suggested that the disturbed immunoreactivity of synovial fluid lymphocytes from RA patients may be due to increased OI generated by stimulated neutrophils.
Normal human peripheral blood T lymphocytes activated by concanavalin A (Con A) were fractionated into OKT4+ and OKT8+ populations by complement-dependent cell lysis using OKT8 and OKT4 antibodies, respectively. By using the preferential ability of some, but not all, Con A-activated T cells to form rosettes with autologous erythrocytes, each population was further divided into autorosetting cells and nonautorosetting cells, and thus Con A-activated OKT4+ autorosetting, OKT4+ nonautorosetting, OKT8+ autorosetting, and OKT8+ nonautorosetting cells were obtained. The immune regulatory function of these populations was then investigated using a pokeweed mitogen-driven B cell plaque-forming cell system. These studies demonstrated that (a) autorosetting cells can exert potent suppressor activity regardless of their phenotypes of OKT4+ and OKT8+ antigens, and fail to help B cell differentiation; suppressor function mediated by these cells is radiosensitive; moreover, receptors for autologous erythrocytes may constitute either the interleukin 2 (IL2) receptors themselves or a component of an IL2 receptor-effector complex involved in modulating the growth signal that IL2 transmits to T cells; (b) OKT4+ nonrosetting cells serve adequately as radioresistant helper cells, but are devoid of suppressor cells; and (c) OKT8+ nonrosetting cells are found to lack either suppressor or helper activity, suggesting that they may belong to a T lymphocyte subset distinct from the subsets related to immune regulation. The results lead us, therefore, to the conclusion that there may exist functional heterogeneities among both the OKT4+ and OKT8+ populations; these heterogeneities can be dissected by virtue of the autologous erythrocyte rosette technique.
The autologous mixed lymphocyte reaction (MLR) is thought to be part of a regulatory role of T cells on B cell function. OKT4+, but not OKT8+, cells can proliferate in response to autologous non-T cells. Moreover, the OKT4+ cell population activated early in the course of autologous MLR functioned as inducer cells for the differentiation of B cells, whereas later in the response, the activated OKT4+ cells were particularly enriched in suppressor cells. A part of the autologous MLR appears to be an important pathway for the activation of feedback suppression mechanisms among cells contained within the OKT4+ populations. Patients with systemic lupus erythematosus (SLE) were studied with regard to the following OKT4+ cell functions in vitro after activation in the autologous MLR: a) proliferative response, and b) helper and suppressor activities for differentiation of B cells. A marked reduction in the proliferative response of OKT4+ cells was observed in SLE patients. SLE OKT4+ cells activated in the autologous MLR could function as helper cells but could not exert any suppressor activity. This OKT4+ cell abnormality was present regardless of the disease activity, and occurred in the absence of autoantibodies including anti-T cell antibodies. Instead, SLE anti-T cell antibodies could preferentially eliminate cells bearing the OKT8+ phenotype characteristic of suppressor cells in populations of normal T cells. These results suggest that the defect in the suppressor circuits among OKT4+ cell populations is intrinsic to SLE lymphocytes and that the OKT8+ suppressor T cell defect is caused by antibodies produced by the B cells of SLE patients.
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Abnormalities of concanavalin A-induced suppressor activity and autologous mixed lymphocyte reaction (which is part of the regulatory role of T cells on lymphocyte functions) were observed in patients with preactive Behçet's disease. However, both the functions returned to normal when the patients entered an active or inactive phase of disease. Thus, a diminution of suppressor function appears to be necessary for the initiation or potentiation of autoimmune and/or inflammatory abnormalities in Behçet's disease. Results of studies of T cell subsets and their functional analysis in patients with preactive Behçet's disease provide further evidence in support of this hypothesis.
When human T cells were treated with neuraminidase from Vibrio cholerae, the capacity of T cells to form rosettes with autologous erythrocytes was markedly enhanced. The neuraminidase-treated T cells wee separated with autologous erythrocytes into autorosetting and nonrosetting cell populations, and these two populations examined for their reactivity to mitogens and B cells and for their regulatory activities. Autorosetting T cells proliferated poorly in response to mitogens and autologous and allogeneic B cells; these cells were particularly enriched for cells capable of becoming concanavalin A-induced suppressor cells. Nonrosetting T cells capable of most actively proliferating in response to the mitogens and the B cells failed to exhibit such suppressor function after concanavalin A activation. Coculture experiments between autorosetting and nonrosetting cells further demonstrated that the nonrosetting T cells were able to potentiate the proliferation of the autorosetting T cells with concomitant expression of the suppressor properties.
Studies were performed using an in vitro assay system to determine whether or not methyl-B12 could affect human T-cell function. When T cells were stimulated with phytohemagglutinin and allogeneic B cells, methyl-B12 did not enhance T-cell proliferation. In contrast, remarkable enhancing effects of methyl-B12 on the proliferative response to concanavalin A (Con A) and autologous B cells at suboptimal concentrations were observed, ranging from 0.1 to 10 micrograms/ml. Concentrations of methyl-B12 sufficient to enhance cellular proliferation were able to enhance the activity of helper T cells for immunoglobulin synthesis of B cells by pokeweed mitogen. Furthermore, the presence of methyl-B12 significantly potentiated the induction of suppressor cells in Con A-activated cultures. These results suggest that methyl-B12 could modulate lymphocyte function through augmenting regulatory T-cell activities.
Patients with systemic lupus erythematosus (SLE) were found to have in their plasma antibodies specific for desialized T cells. Adsorption studies with intact or desialized T cells indicated that SLE anti-T cell antibodies consisted of two populations with different target cell specificities, one capable of recognizing unique determinants on desialized T cells and another able to bind to both intact and desialized T cells. Normal T cells did not remove the antibodies specific for desialized T cells. moreover, the antibodies to desialized T cells were not removed by adsorption with either desialized non-T cells or desialized erythrocytes. Thus, the antibodies to desialized T cells recognize a determinant that is unique to a T cell subset and also includes a sugar. Inhibition studies with various sugars indicated that lactose was the most potent inhibitor of antibody binding. The anti-desialized T cell antibody appears to recognize a T cell determinant which includes lactose, probably in the form of a beta-galactosyl residue, but which also includes additional T cell determinants. The antibodies to desialized T cells were found to bind preferentially to concanavalin A-induced autorosetting T cells, which had been already demonstrated to contain suppressor effector cells. Indeed, such antibodies were effective in eliminating suppressor effector function without interfering with T cells necessary for such activation (such as precursor or inducer cells). Finally, studies of patients with SLE yielded a highly significant correlation (r = 0.92) between impaired suppressor effector function of their cells and the presence of antibodies to desialized T cells in their plasma.
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