It has been reported that injection of Transfer Factor (TF) enhances cellular immune reactions not only in patients with a variety of immunodeficiency but also bronchial asthma and atopic dermatitis. We studied the effects of oral administration of TF on nine patients with intractable atopic dermatitis and two patients with recurrent aphthous stomatitis having a dietry link. All of them showed somewhat decreased cellular immunity. Clinical symptoms of these disorders were prominently improved following the oral administration of TF. However, the interval before the appearence of effectiveness varied in each case from 1 time administration to 5 times. TF induced increased serum levels of IgG and IgA immunoglobulin. On the other hand this therapy reduced serum levels of antigen specific IgG antibodies. Our results suggest that oral administration of TF is as effective as injection therapy to control the symptoms of children with intractable atopic dermatitis and recurrent aphthous stomatitis having some decreased cellular immunity.

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Dendritic cells (DC) were isolated from peripheral blood of patients with systemic lupus erythematosus (SLE) and nodrmal donors. Surface antigens of the DC were analyzed by indirect immunofluorescence by means of monoclonal antibodies. Surface expression and stimulatory function of the DC in the mixed lymphocyte reaction (MLR) were also investigated. DC from both SLE patients and normal donors were positive for HLA-DR antigen and C3bi receptor, but did not express surface immunoglobulin, Fc receptor or CD3.
In the autologous MLR, stimulating DC were markedly decreased in patients with SLE compared with normal donors.
In the allogeneic MLR it was shown that DC from SLE patients were poorer stimulators of allogeneic T cells from normal donors and from other SLE patients; however T cells from SLE patients were not such poor responders to allogeneic DC from normal donors.
These findings suggests a defect in peripheral blood DC in patients with SLE.

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Changes in cytotoxic activity were studied in lymphocytes cultured with the addition of tumor cells treated to preserve tumor antigenicity. AH109A cells were treated with (1) Mitomycin C, (2) 3M KCl, (3) ultrasound and (4) lyophilization and these treated cells were added to culture systems of lymphocytes from Donryu rats. The lymphocytes cultured with lyophilized antigen resulted in the highest cytotoxic activity.
Human lymphocytes cultured with lyophilized autologous ascitic cancer cells demonstrated a higher cytotoxicity against the same cancer cells than the corresponding cells cultured without the antigens.
In the cross reactive test using BALB/c mouse lymphocytes and several kinds of tumor cells, lymphocytes cultured with lyophilized antigen demonstrated an antigen-specific cytotoxicity.
This data suggests that autoimmunotherapy using lymphocytes cultured with lyophilized tumor cells appears to be clinically useful for cancer therapy.

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Raji cells derived from Burkitt lymphoma, were mutated in vitro with ethylmethanesulfonate (EMS) and selected in the presence of 1×10^-4M of 6-thioguanine (6-TG). The most rapidly growing 6-TG-resistant clone was obtained and named Raji 6-TG^R cells. Furthermore, plasmid vector pSV2 neo gene was transfected to Raji 6-TG^R cells by liposomes-mediated gene transfer technique. The transfected cells were selected by neo selective medium (10% FCS-RPMI 1640 medium supplemented with 1mg/ml Geneticin). The fastest growing neo-resistant clone, Raji 6-TG^Rneo^R cells were established. The characteristics of Raji 6-TG^R-neo^R cells were as follows;
1. Raji 6-TG^R-neo^R cells were deficient in hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity, because this cell line was sensitive to HAT (H: 1×10^-4M, A: 2×10^-8_??_1×10^-7M, T: 1.6×10^-5M) selective medium.
2. Raji 6-TG^R-neo^R cells did not secrete human Ig in culture medium, when tested by enzyme-linked immunosorbent assay (ELISA).
3. Raji 6-TG^R-neo^R cells were fused with B cells, PWM stimulated B cells (PWM-B cells) or EBV transformed B cell line (CESS cells), and selected by a new selective medium (HAT-neo). The percentage of cell growth was as follows, B cells (2%), PWM-B cells (5%) and CESS cells (11%).
These results suggest that Raji 6-TG^R-neo^R cells are suitable for production of human B cell hybridomas in the new selective medium (HAT-neo).

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The responses to IFN-γ of the peripheral blood mononuclear cells (PBMC) in hemodialysis (HD) patients were studied as an index for cellular activity in the cultured supernatant and intracellular β2-microglobulin (β2-m) amount, and the following results were obtained.
1) The amount of spontaneous β2-m production in tne cultured supernatant of PBMC was observed not to have any difference between healthy individuals and HD patients.
2) After incubating for 96 hours adding 100 JRU/ml of IFN-γ, it was noted that β2-m amount in the supernatant in HD patient group with more than 60mg/l of serum β2-m level was significantly lower compared with healthy individuals.
3) The percent increase of cellular β2-m in HD patients also showed a tendency to be lower.
4) In order to evaluate the influence of β2-m on the decrease of production capability of β2-m, influence on β2-m production of PBMC was examined by testing PBMC preincubated for 2 hours with concentrations of 20mg/l and 100mg/l of purified β2-m. However, no influence was noted.
5) Levels of IL-1 β and IL-2 in the cultured supernatant were measured by using RIA and ELISA methods respectively, these were not detectable using these methods.
From the avove-mentioned results, decrease of the response of PBMC to IFN-γ was noted in HD patients with more than 60mg/l of semm β2-m amount, and suppression of host defence mechanisms was suggested.

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To characterize the insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) in terms of the complement system, some components of the system as well as the related substances and indics were studied.
CH50, C3, C4 and C3bINA significantly increased in both IDDM and NIDDM compared with the non-diabetic healthy control. ACH50 was also elevated in NIDDM, whereas it was similar in IDDM and the control. Besides, serum concentration of C3d, a breakdown product of C3, was higher in IDDN than NIDDM and the healthy control, but that in NIDDM was not different significantly from the control. β1Hgl was not different among IDDM, NIDDM and non-diabetic control.
These findings suggest that there is a high level of complements in both types of diabetes mellitus, but the complement activation seems to be enhanced in IDDM compared with NIDDM.

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Spleen cells (SC) obtained from gastric and esophageal cancer patients were tested for natural killer (NK) cell activity against K 562 cells and non-specific suppressor cell activity against lymphocyte proliferative response to phytohemagglutinin, in comparison with those of splenic venous blood lymphocytes (SVL) and peripheral blood lymphocytes (PBL). Furthermore, in vitro effects of biological response modifiers (BRM), recombinant interleukin-2 (IL-2), human lymphoblast interferon (IFN) or a streptococcal preparation, OK-432, on the augmentation of NK cell activity were investigated in the presence of suppressor cells. In PBL obtained from cancer patients, NK cell activities tended to decline according to the advance of the disease, and positive suppressor cell activities were frequently detected in advanced cases. Similarly, positive suppressor cell activities were frequently detected in SVL and SC from advanced cancer patients, though high NK cell activities were observed in several advanced cancer patients with negative suppressor cell activities. NK cell activities of PBL in normal control donors were strongly augmented by IL-2, IFN or OK-432. Similarly, these agents exhibited the capacity to augment NK cell activities of PBL and SVL in cancer patients. On the other hand, NK cell activities of SC were similarly augmented by IL-2 or OK-432, not by IFN, in cancer patients. Moreover, NK cell activities of PBL, SVL or SC with negative suppressor cell activity were augmented by these BRMs in many cases. However, incidence of cases with significantly augmented NK cell activity by these agents in PBL, SVL or SC with positive suppressor cell activity tended to be lower than that with negative suppressor cell activity. These results suggested that NK cell activity might be regulated by non-specific suppressor cells, and the presence of suppressor cells might affect the augmentation of NK cell activity by BRM in circulating blood lymphocytes and also in spleen cells in cancer patients. IL-2 and OK-432 might be effective on the enhancement of immunological response in the presence of suppressor cells, but IFN might not.

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Massive hepatic cell necrosis can be induced in mice by an intravenous injection of Propionibacterium acnes (P. acnes) followed by an intravenous injection of a small mount of lipopolysaccharide (LPS) 7 days later. Using this experimentally-induced acute hepatic failure model, the products of tryptophan (TRP) metabolism during hepatocytotoxicity were studied. As a result, in acute hepatic failure-induced mice, blood indoleacetic acid (IAA) level increased before the increase in serum transaminase level, and its peak was seen 21 hours before that of transaminase. In addition, when hepatic cells separated from the mice were loaded with TRP and cultured with the cytotoxic factor produced from activated liver adherent cells, IAA level of the hepatic cells increased remarkably.
These results suggest that during hepatocytotoxicity, the change from kynurenine to nicotinamide by the major pathway of TRP metabolism may be inhibited, and that the pathway from TRP to tryptamine to IAA may be impaired.

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A considerable amount of research has been reported on LAK adoptive immunotherapy (LAK AIT). In order to evaluate the effect of LAK cells and interleukin-2 (IL-2), most investigators have been using highly-immunogenic tumors and showed therapeutic benefit in the treatment of these tumors.
But many of human neoplasms are usually said to be nonimmunogenic. So both highly-immunogenic tumors and nonimmunogenic tumors were used, and the difference of the effect of IL-2 between these tumors were studied in our in vitro and in vivo experiments. The effects of IL-2 against highly-immunogenic and nonimmunogenic tumors were checked by in vitro cytotoxicity assays, and it was shown that IL-2 increased the cytolytic activity against both of these tumors. These activations are thought to be due to elevation of nonspecific immunity by IL-2.
Against highly-immunogenic tumors, if spleen cells immunized with highly-immunogenic tumors were used for induction of LAK cells, the cytolytic capacity was higher than that of not immunized spleen cells. In the case of LAK AIT models against highly-immunogenic tumor bearing mice, the most effective group was the group using LAK cells induced from immunized spleen cells. This fact showed that IL-2 elevated LAK activity and CTL, so using immunized cells was the most effective case.
In the case of nonimmunogenic tumor, activated specific immunity was unable to be detected. But nonspecific immunity was increased and therapeutic benefit was also signi-ficantly obtained against nonimmunogenic tumors in both in vitro and in vivo assays.
According to these results, LAK AIT is considered to be useful against human cancer which is thought to be nonimmunogenic.

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We report a 55-year-old male patient with HBeAg positive hepatocellular carcinoma who showed twice clear-cut and prolonged decrease in serum alfa-fetoprotein (AFP) level with administration of recombinant IL-2 (rIL-2). From Sep. 2 to 8 and from Oct. 14 to 20 in 1985, 500 units (1.5×10⁵ NCI unit) of rIL-2 was dripped intravenously every day. Serum AFP level decreased abruptly in the first 18hr. with IL-2 administration only of 500 units. It remained low upto Sep. 17. and returned to that of before treatment. On the second confirming trial, serum AFP level decreased abruptly again and remained low for 12 days. Considerable reduction of LAK activity in this patient was recovered by in vivo administration of IL-2. Precise mechanisms of this drastic decrease of AFP level are in further investigation. But prolonged AFP suppression may partially be contributed to induction of LAK activity besides activated T cell proliferation against HCC. And the early effect, definite reduction of serum AFP in the first 18hr., may partially come from suppressive effects of IL-2 on HCC as IFN on PLC/PRF/5 hepatoma cell line.

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A 56-year-old male patient suffering from hyperthyroidism had been treated with antithyroid drug and his thyroid function turned to euthyroid. However, he suffered from visual disturbance with his visual acuity of 0.01 and exophthalmus, which were diagnosed as dysthyroid optic neuropathy (DON). Post orbital injection of corticosteroid and oral administration of prednisolone up to 100mg at maximum per day were not effective. Therefore, he was treated with 2 courses of plasmapheresis (4 times/2 weeks each) and corticosteroid pulse therapy with drip infusion of 3, 000mg/3 days of methylprednisolone. His visual acuity improved up to 0.8 and exophthalmus was reduced with a disappearance of extraocular muscle enlargement on CT.
Serologically, anti-TSH receptor antibody decreased to 10% from 64.5%, and serum IgG levels increased to 720mg/dl from 420mg/dl. A ratio of OKT4/OKT8 improved to 3.0 from 0.8. These results would indicate that the observed disappearance of extraocular muscle enlargement and the improvement of visual acuity could reffer to the normalization of his immunological disorders by plasmapheresis and steroid pulse therapy.

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A 38-year-old man who had been treated as a patient with systemic lupus erythematosus (SLE) during the last 12 years was admitted to the Kawasaki Municipal Hospital in February, 1986, because of high fever. Anemia due to both autoimmune hemolytic anemia and follic acid deficiency was confirmed. After the administration of prednisolone together with follic acid, the patient was recovered from anemia.
In July, 1986, jaundice appeared abruptly and liver function deteriorated. After the administration of prednisolon, jaundice and liver function improved slightly. But in 1987, total bilirubin increased up to 30-53mg/dl. Despite therapeutic trials including high dose of steroid and plasma exchange, liver dysfunction continued. Finally hemorrhagic tendency, hypoproteinemia and consciousness disturbance appeared and the patient died on February, 1987.
An autopsy revealed; There were primary cholestatic liver fibrosis, focal segmental prolif-erative lupus nephritis and the Libman-Sacks endocarditis. Scince the severe liver dysfunction is unusual in the patient with SLE, we report this rare case.

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Human adjuvant disease is a connective tissue disease similar to disorder occurring after cosmetic surgery by the use of foreign substance. No male patient with this disease have been reported until now. We recently observed a 49-year-old man developed seronegative rheumatoid arthritis and non-Hodgkin's lymphoma 30 years after the injection of foreign substance into the penis.
The patient visited our hospital because of difficulty of neck movement and bilateral omalgia. He also had polyarthritis in the bilateral carpal and knee joints with bone erosions. The synovial fluid from a inflamed knee joint failed to form sufficient mucin clotting. It did not contained malignant cells. By histological examination, foreign body granulomas were noted not only in the injected site but also in the inguinal lymphnodes. The foreign substance was chemically identified as paraffin. The removal of the substance produced no significant improvement in his clinical course, but by the administration of 10mg daily prednisolone improved his arthralgia dramatically. Four months after discharge, he noted a small nodule in the left cervical region which was diagnosed as non-Hodgkin's lymphoma, diffuse large cell type by histological examination. He was treated with ⁶⁰Co irradiation and chemotherapy. The tumor regressed and complete remission was induced after 2 months.
Several clinical features of this patient were compatible with human adjuvant disease reported in female patients. It is also interesting that he subsequently developed malignant lymphoma.

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In this report, we described a patient with progressive systemic sclerosis (PSS) died from massive hematoemesis due to an aortoesophageal fistula.
This patient was a 71 years old woman. She had Raynaud's phenomenon since 20 years before and sclerodactyly and swallowing disturbance were gradually developed. She admitted to the hospital because of upper abdominal pain and loss of appetite. On the 10th hospital day, she fell into shock with severe back pain and died from the following massive hematoemesis. In the autopsy, an esophageal ulcer was present in the dilated lower esophagus and a hole of 1mm in diameter reached to the aorta.
Aortoesophageal fistula from reflux esophagitis was extremely rare. In this case, it was seemed that fistula formation was caused by fibrosis in the subcutaneous tissue and muscle atrophy of lower esophagus.

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To assess the immunochemical characters of suppressor factor from human decidual cells (DC), serum free culture supernatants of DC were analyzed by high performance liquid chromatography (HPLC). Early pregnant decidual tissue was dispersed into a single cell by enzyme digestion using collagenase and DNase, and purified by Percoll^® discontinuous density gradient method to avoid contamination of mononuclear lymphocytes and macrophages. 3×10⁶/ml of DC were cultured in RPMI 1640 medium without fetal calf serum (FCS) for 48 hours at 37°C, and supernatants were harvested. The suppressor activity of culture supernatants were assessed by mixed lymphocyte reaction (MLR). Thirty two percent suppression was obtained by the addition of culture supernatants (50% volume) to MLR. To purify the suppressor factors in the supernatants, serum free culture supernatants were applied to gel filtration (HPLC) and the suppressor activity of each fraction was assessed by MLR. Fraction (Fr) 25 (between MW 43, 000 and 67, 000) displayed remarkable immunosuppressive activity, namely 46% inhibition in MLR. These results clearly demonstrated that DC secreted suppressor factor molecular weight of which was between 43, 000 and 67, 000, thereby protecting the fetus from maternal immunity.

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