Cell mediated immunity in patients with subacute sclerosing panencephalitis (SSPE) was examined. Interleukin 2 (IL 2) production induced by phytohemagglutinin (PHA) and autologous mixed lymphocyte reaction (AMLR) was almost normal except for a patient, whose IL 2 production was decreased in stimulation with PHA. In contrast, IL 2 responsiveness of T cells in stimulation with PHA was decreased in one patient, and IL 2 responsiveness in AMLR was diminished in all three patients tested. As the expression of Mo 1 and HLA-DQ was decreased in three and two patients respectively, non-T stimulator cells were suggested to be unable to induce IL 2-responding T cells in AMLR. Natural killer (NK) activity against K 562 target was impaired in two patients, but was retained in one patient. Lymphokineactivated killer (LAK) activity induced in 4-day-cultured lymphocytes was reduced in all three cases. In two cases whose LAK activity is markedly reduced, expression of Leu 19 or CD 20 antigen, a surface marker of precursors of LAK cells, was decreased. The combined data showed that decreased IL 2 responsiveness of T cells and LAK activity may reflect reduced cell-mediated immunity induced by measles virus infection and a defective defense mechanism against virus responsible for the development and progression of SSPE.

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By means of monoclonal anti-C1q and anti-C3d ELISA systems, circulating immune complexes (CIC) of patients with various collagen diseases were measured.
The positive frequencies and mean values of CIC detected by anti-C1q were 94% and 145.8μg/ml in active SLE, 50% and 52.5μg/ml in inactive SLE and 56.8% and 58.5μg/ml in RA.
On the other hand, CIC detected by anti-C3d were 67% and 20.0μg/ml in active SLE, 14% and 2.7μg/ml in inactive SLE and 21.6% and 6.1μg/ml in RA.
Levels of CIC detected by the both systems correlated positively with titers of anti-DNA antibodies and negatively with titers of serum CH50 in SLE.
In RA, levels of CIC detected by anti-C3d correlated positively with ESR and CRP, whereas those by anti-C1q did not. No correlations between levels of CIC detected by the both systems and titers of RF were observed.

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We have reported that B cell differentiation factor (BCDF) might contribute to the immunological abnormalities in lupus erythematosus, one of autoimmune diseases. In order to clarify the role of BCDF in autoimmune Hashimoto's thyroiditis, we examined autoantibody production by B cells in response to recombinant B cell stimulatory factor-2 (BSF-2).
B cells of peripheral blood from patients with Hashimoto's thyroiditis and normal controls were separated by Ficoll-Conray density centrifugation, adhesion to FCS-coated Petri dishes and E-rosetting. Hundred thousands B cells were cultured with 0_??_40 U/ml BSF-2 for 3_??_12 days in microculture plates. Anti-thyroglobulin antibody (anti-Tg) and total IgG in culture supernatant were assayed by sensitive Biotin-Avidin ELISA and conventional ELISA, respectively. Results were expressed as ELISA Index based on a standard serum. Coefficients of variation of intra-assay and interassay were 8.0 and 10.7% respectively.
When the effect of BSF-2 (0_??_40 U/ml) on B cells for the production of anti-Tg was tested, apparent stimulatory effect of BSF-2 was observed at the concentration of 10 U/ml and 20 U/ml. Since there was no significant difference between 10 and 20 U/ml, 20 U/ml of BSF-2 was used for the following experiments.
Kinetics analysis of anti-Tg production was studied in the presence or absence of BSF-2 up to 12 days. Although normal B cells did not produce anti-Tg, Hashimoto's B cells produced significant amount of anti-Tg in response to BSF-2 at 9 days (30.3±4.1 vs. 22.3±3.9 ELISA Index, p<0.05). Total IgG production by Hashimoto's or normal B cells were not enhanced by BSF-2 stimulation. These result suggested that peripheral blood B cells from patients with Hashimoto's thyroiditis are already activated for the production of anti-Tg in vivo and responded to BSF-2 without any pre-treatment.

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The effect of long term treatment with various immunomodulating drugs for rheumatoid arthritis (RA) was retrospectively evaluated by the method of life-table analysis. Four hundreds seventy seven patients with RA in total included 95 cases treated with bucillamine (BU), 84 with sulphasalazine (SASP), 149 with D-penicillamine (DP), 32 with methotrexate (MTX), 103 with auranofin (AF) and 54 with lobenzarit disodium (CCA). The longest follow up period reached to 42 months.
The longer durations of the treatment than average were observed in cases with MTX and DP, on the other hand, the shorter durations were seen in AF and CCA groups. As to BU and SASP, the durations of the treatment were intermediate between those 2 groups.
The main reasons of discontinuation of the drug were the adverse effect in BU and the little therapeutic effect in AF. Some of the discontinuations due to severe adverse effects were seen in groups of BU, SASP and DP.
These results obtained by the life-table analysis were consistent with our clinical impressions on drugs and revealed that the life-table analysis would be useful for the long term comparative studies on the slow acting drugs.

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There is a well documented association between rheumatoid arthritis (RA) and the HLA-DR4 and DRw53 in many racial groups. Recently, much interest in the genes and their products in HLA class III region has been generated by their possible involvement in the development of autoimmune diseases including systemic lupus erythematosus. In this study, the allotypes of complement C4A, C4B and properdin factor B, which are coded for by genes in the class III region, were investigated in Japanese RA patients and controls. The frequency of C4B5 was significantly higher in RA patients, especially in male as compared with female patients, than that of the controls. Since a strong linkage disequilibrium among genes of C4B5, DR4 and DRw53 is reported in Japanese, and since RA patients in other ethnics are not associated with C4B5, the allotype, C4B5, will not have a direct role for the development of RA. We further analysed restriction fragment length polymorphisms of the genes in the HLA class III region in RA patients and controls by Southern blot method using C4 or 21-hydroxylase cDNA probe and restriction enzymes, such as BamHI, TaqI, HindIII and KpnI. When the C4 probe was used, HindIII 6.0 and 10kb fragments were observed only in C4B5-positive persons including patients and controls. Some of the RA patients were deficient for TaqI 6.0kb fragment which was present in all of the controls tested. However, we could not identify any specific bands for RA patients.

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The two cases with malignant liver tumors were investigated to show the in vivo distribution of tumor-infiltrating lymphocytes (TIL) transferred via hepatic artery.
Recombinant interleukin-2 and anti-CD3 antibody activated TIL, labeled with ¹¹¹In, were injected into the hepatic artery through an Infuse-A-Port. In a patient with hepatocellular carcinoma, the radioactivities in the area corresponding to tumor site were significantly higher than those in the non-cancerous portion of the liver, at least, until 48 hours after injection. Similar result was observed in a patient with metastatic liver tumors from rectal cancer.
This preliminary result indicates that an intra-arterial transfer will be preferable to acquire further accumulation of TIL at tumor sites in the liver.

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Recently, immunotherapy for leukemia have been carried out with chemotherapy in many institutes including our laboratory. This study was examined ex vivo adoptive immunotherapy (AIT) for leukemia. Short time incubation of lymphokine activated killer (LAK) cells with CD3 monoclonal antibody (moAb) in effector phase resulted in augmentation of LAK activity in 10 of 15 patients with acute leukemia. There was correlation between LAK activity and the expression of Fc receptor on the leukemia cells. Though treatment with CD3 or CD2 moAb for LAK cells could enhance the level of calcium influx, and CD3 moAb could augment LAK activity, but CD2 moAb failed to augment. An interesting observation was the significant activation of LAK cells by stimulation with CD3 moAb, but not by CD2 moAb. CD3 moAb dependent activation of LAK cells may determined by several factors including the expression of Fc receptor on leukemia cells, it was possible that cross-linking of CD3 moAb on LAK cells and Fc receptor on leukemia cells. Furthermore, there was possibility CD3 moAb specific signal transduction induced augmentation of killing activity. This CD3 moAb induced effector cell has strong anti-leukemia effect and may play a significant role in the AIT.

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In this report, we described a patient with rheumatoid arthritis (RA) who complicated with secondary amyloidosis and myelodysplastic syndrome (MDS). The patient was a 65 years-old woman. She was diagnosed rheumatoid arthritis at 50 years old.
In August, 1987, she admitted our hospital for proteinuria and edema. She was diagnosed the complication of secondary amyloidosis by gastric and rectal biopsy. Her anemia progressed rapidly, since march, 1988, leucopenia and thrombocytopenia also appeared. Then she was diagnosed MDS by bone marrow examination.
Using a set of synthetic oligonucleotide probe, we found the point mutation at codon 13 of N-ras gene in bone marrow cells from the patient.
It was suggested that the activated N-ras gene by this point mutation is closely related to the pathogenesis of MDS in this patient.

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A case of serologically highly suspected systemic lupus erythematosus (SLE) with pancytopenia because of hypoplastic bone marrow was reported. A 38 year-old female was admitted to Sapporo Medical College Hospital because of general malaise and body weight loss. On admission, laboratory examinations revealed severe pancytopenia, positive antinuclear antibody, positive anti-DNA antibodies, high titer of anti-Sm antibodies and anti-RNP antibodies, hypocomplementemia, and severe hypoplastic bone marrow. The diagnosis of SLE (three items of the 1982 revised criteria was present in this case) with aplastic anemia was highly suggested.
Since a complement-dependent serum inhibitor of the growth of the patient's bone marrow cells in vitro was detected in patient's desease phase serum, it was suggested that the marrow aplasia was mediated by autoimmune mechanisms.

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A patient with systemic lupus erythematosus (SLE) in whom hoarseness developed during an acute exacerbation of the disease was reported. Laryngoscopic examination showed diffuse edema and scarring of the larynx. Histrogic examination revealed mononuclear cells infiltration. Hoarseness with other disease activities improved by corticosteroid therapy. From these findings, we diagnosed this acute laryngitis as lupus laryngitis which has not been reported in Japan. Involvement of the larynx in SLE is rarely mentioned in published reports. The symptoms of lupus laringitis range from hoarseness to life-threatening respiratory distress. We should pay attention to laryngeal symptoms in patient with SLE as lupus laryngitis.
Furthermore, in this case, onset of SLE occurred 10 days after estrogen administration. Recently experimental studies have clearly demonstrated harmful effects of estrogens in NZB/NZW F₁ mice. However, a possible influence of estrogen on the activity of human lupus still remains a matter of discussion. This case is very interesting to consider the clinical effect of estrogen to human SLE.

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