We studied the effect if immunoregulatory drugs on the generation of concanavalin A (Con A)-induced suppressor activities of human peropheral blood T lymphocytes from healthy individuals. CCA (carboxyphenyl chloranthranilic acid; 0.5 and 50 μg/ml) and levamisole (1 and 100 μg/ml) were used as immunostimulants. Prednisolone sodium hemisuccinate (0.01 and 1 μg/ml) was used as the immunosuppressant. For the generation of suppressor T lymphocytes, purified human T lymphocytes were incubated with 2μg/ml (suboptimal dose) or 10μg/ml (optimal dose) of Con A for 3 days in MEM containing 10% FCS in the first culture, in the absence or presence of low or high concentrations of drugs. In a separate experiment, drugs were added to previously Con A-activated suppressor T lymphocytes and the preparation was cultured for 24 hours. The suppressor activity was then evaluated (1)the T lymphocyte proliferation stimulated with allogeneic mononuclear cells, (2)the B lymphocyte proliferation stimulated with pokeweed mitogen and (3)IgG synthesis rates of B lymphocytes stimulated with pokeweed mitogen, by a second six day culture. All drugs at each concentration showed a tendency to enhance suppressor activities of T lymphocytes stimulated with suboptimal doses of Con A. Suppressor activity on the IgG synthesis rates was statistically enhanced with each drug, except for high concentrations of CCA. Low concentrations of levamisole and CCA also statistically enhanced the T lymphocyte proliferations and B lymphocyte proliferations, respectively. In contrast, suppressor activities of T lymphocytes stimulated with optimal doses of Con A were not enhanced, rather were inhibited by certain experimental conditions. Very few of the drugs had any effect on the previously generated suppressor T lymphocytes. Thus, we concluded that immunoregulatory drugs, including immunosuppressants as well as immunostimulants do enhance suppressor activity of suppressor T lymphocytes, under selected conditions.

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This study was made to clarify the effects of institutional therapy upon children with so-called "intractable asthma" after discharge. Questionnaires were sent out to 62 asthmatic children who had been discharged from our institute during the period between December, 1975 and March, 1978. Forty-seven children responded to the questionnaires, and 37 of them underwent medical examination and psychological tests administered by us. The children were divided into 3 groups according to their asthmatic conditions after discharge from our institute; Group I consisted of 17 subjects who had had no asthmatic attacks after discharge; Group II consisted of 20 subjects who had had attacks, but had not received steroid hormones; and Group III consisted of 10 subjects who had had to receive steroid hormones. The results of our study can be summarized as follows: 1)There was no significant difference among the three groups with regard to sex, onset of asthmatic attacks, incidence of allergic disease in family history, positive responses to skin test using certain popular allergens or serum IgE levels. 2)Subjects who had had no asthmatic attacks while in our institute were found in greater numbers in Group I than in Group II (p<0.05) or Group III (p<0.001). 3)Subjects who had had to receive steroid hormones while in the institute were found in greater numbers in Group III than in Group I (p<0.05). 4)Subjects who had received steroid hormones before admission to our institute were found in about equal numbers in the three groups. 5)The mean of the threshold amounts of inhaled acethylcholine needed to decrease FEV_<1.0> by more than 15% was not significantly different in Group I from Group II. 6)The mean of the threshold amounts of acethylcholine measured after discharge was significantly lower than it was while they were in our institute. The degree of decrease of the threshold amounts was larger in Group II than in Group I. With respect to Rosenzweig's picture-frustration study, all three groups showed impunitive reactions and did not show extrapunitive reaction. Group II showed a high Group Conformity Rating (GCR). Group III did not show intropunitive reactions. Group I continued with their training of their own accord after discharge, but Group III did not.

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Correlations were studied between changes in blocking antibody titers and clinical course in 62 patients with positive skin test to house dust who had receives immunotherapy with house dust. Results are as follows. 1.Blocking antibodies to house dust were detected before the immunotherapy was given. Blocking antibodies were detected in about 60% of patients who received at least 40 doses of immunotherapy. 2.Blocking antibody titers varried during the immunotherapy. 3.There was no correlationship between changes in blocking antibody titers and clinical symptoms. 4.Changes in blocking antibody titers paralleled (p<0.001) changes in thresholds on skin test in about 80% of patients. 5.Clinical symptoms were less serious in patients with high thresholds on the skin test. The latter did not correlate with frequency of the attacks. Changes in the blocking antibody titers seemed not to correlate with clinical symptoms but correlated with changes in threshold on the skin test.

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Hamilton had described a solid-phase radioimmunoassay method for quantitation of antigen-specific IgG antibody with ^<125>I-protein A system using Sepharose-4B. It was attempted in this study to use paper disc in its system as a substitute for Sepharose-4B. This modified procedure could produce the successful results in quantitation of antigen-specific IgG antibody, possessing the most favorable advantage to be applied to many kinds of crude antigens. As the specificity and reproducibility of our modification was confirmed, IgG antibodies to mite, Japanese cedar pollen, wormwood pollen or orchard grass pollen were measured in untreated and treated patients with nasal allergy or asthma. The levels of IgE and IgG antibodies specific for an antigen were not correlated in many cases. The mean value of IgG antibodies to mite was remarkably higher than that of IgG antibodies to pollens. IgG antibodies to mite were also detected in normal individuals. Rise in the levels of IgG antibodies was prominent only in mite-antigen injected cases and those were related to the improvement of clinical signs. It was considered, however, that it was principally mediator cell stability that was acting to suppress the allergic conditions during immunotherapy in pollinosis, especially in Japanese cedar pollinosis.

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Serum-specific antibodies against mite (Dermatophagoides farinae) allergen were measured by indirect ELISA using antisera specific for IgG, IgE and four subclasses of IgG. Raised titers of specific IgG to mite allergen were found in 15 of 45 (31.9%) patients having only atopic dermatitis (pure AD group), in 19 of 27 (70.4%) patients with atopic dermatitis associated with allergic respiratory disease(s) (AD+ARD group), and in 19 of 30 (63.3%) patients with bronchial asthma not associated with AD (pure BA group). Elevated specific IgE titers in these three groups were found in 12.8%, 44.4% and 40.0% of the patients, respectively. When pure AD group and AD+ADR group were subdivided according to the presence of family history of atopic disease, the subgroup of negative family history in pure AD group showed significantly depressed titers of specific IgE, whereas the subgroup of positive family history in AD+ADR group showed abnormally high titers of both specific IgG and IgE. Specific IgG4 antibodies were also found in the three groups, in distributions similar to that of specific IgG. A good correlation between the severity of atopic dermatitis and the specific antibody titers of IgG, IgE and IgG4 was observed.

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The present studies describe effect on proliferation of BHK cells in cultures by transfer factor (TF, human leukocyte dialyzable extracts) which was produced for clinical use in Japanese Red Cross Central Blood Center by the method of Lawrence, et al. One vial of TF powder was dissolved with 2ml of culture midum (Eagle MEM+5% fetal calf serum) and its solution was used as 0.5 unit/ml concentration. Different concentrations of TF solution were added to culture plates. The 100 μl of suspension of BHK cells (BHK/21, Flow Co. Ltd.) at a concentration of 5×10^4/ml in culture medium, was added to a well of microplate with or without TF. The final concentrations of TF in the wells were 0.0125-0.25 unit/ml, respectively. Cultures were incubated for 3 days in 5% CO_2, at 37℃. On the third day, proliferated cell numbers were counted. The marked proliferation of BHK cells in the wells with TF was observed. The optimum concentration of TF on the enhancement of BHK cell proliferation was 0.025-0.05 unit/ml in the final medium compositions. The similar results were obtained on FL cells (Amnion, Flow Co. Ltd.) in cultures. There were no remarkable differences in these effects on the several different lot numbers of TF products. The mechnism of the enhancement of this cell proliferation remains to be elucidated, although it is not likely that the effect may be related to the immunological activities of TF.

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