Dendritic cells (DC) act as accessory cells (AC) in suboptimal concanavalin A (Con A) response. We studied peripheral blood DC function in patients with rheumatoid arthritis (RA). DC of RA patients have dendritic appearance and are positive for HLA-DR antigen and C3 bi receptor. Suboptimal Con A response of RA patients was significantly depressed compared with that of normal subjects (p<0.01). In allogeneic reconstitution experiments, T cells from RA patients were not impaired in Con A response. On the other hand, DC from RA patients functioned abnormally as AC. Thus RA DC dysfunction as AC was shown in suboptimal Con A response.

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Recently, it has been found that human hepatocellular carcinoma (HCC) cell lines secrete fairly amounts of TGF-β. Considering the possible negative effects of TGF-β on the immunotherapeutic regimen, in which we intend to induce LAK cells endogenously by systemic IL-2 infusion, we focused on the analysis of immunosuppressive effects of TGF-β on the generation of human LAK cells. The results were as follows:
(1) TGF-β inhibited LAK cell generation in vitro in a dose-dependent manner at concentration ranging from 120ng/ml. LAK cells, once fully activated, became resistant to the suppressive effects of TGF-β.
(2) Inhibitory effect was most prominent when TGF-β was added 24 hours prior to IL-2 addition. On the contrary, when TGF-β was added 24 hours later than IL-2, TGF-β could not exert enough suppression.
(3) Flow cytometric analysis revealed the differential effects of TGF-β on the expression of IL-2 receptor, α and β chain. In contrast to the marked suppression of membrane-bound IL-2 R α chain, β chain was not down-regulated.
(4) Measurement of soluble IL-2 R level, corresponding to the shedded form of IL-2 R α chain, showed the inhibition of soluble IL-2 R secretion by TGF-β, indicating the overall suppression of IL-2 R α chain production.
All these results suggest that manipulation of the production or the effects of TGF-β derived from malignant cells might be an important aspect for successful immunotherapy.

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In order to analyse the epitope structure of carcinoembryonic antigen (CEA) which could be used for active immunotherapy, seven anti-idiotypic monoclonal antibodies (anti-Id MoAbs) were generated from a BALB/c mouse immunized with anti-CEA MoAb P 1-356, which was prepared from a synthetic peptide of domain I of CEA. These anti-Id MoAbs were divided into 4 groups by cross blocking assay. The MoAbs specifically reacted with MoAb P 1-356 and inhibited the binding of CEA and MoAb P 1-356; they did not react with other MoAbs. These results indicate that all of these anti-Id MoAbs recognized private idiotopes at the combining site of MoAb P 1-356.
Polyclonal anti-anti idiotypic antiserum (Ab 3) induced from anti-Id MoAb M 315 blocked the binding of CEA and ¹²⁵I-labelled MoAb P 1-356 (Ab 1) and reacted with CEA, suggesting that it contains “Ab 1 like Ab 3”. Therefore, we prepared anti-anti-Id MoAbs using anti-Id MoAb M 315. Among 13 candidates, anti-anti-Id MoAb 11 B 2 was chosen, because it inhibited the binding of MoAb P 1-356 (Ab 1) and ¹²⁵I-labelled MoAb M 315 (Ab 2). MoAb 11 B 2 (Ab 3) directly reacted with CEA and competed with MoAb P 1-356 (Ab 1) in the competition assay. Direct binding assay using purified ¹²⁵I-labelled MoAb 11 B 2 revealed that it reacted not only with purified CEA from cells, but also with CEA synthetic peptide P 1. In addition, MoAb 11 B 2 (Ab 3) reacted with both CEA-producing cultured cells and colonic cancerous tissues in immunostaining. These results indicate that anti-anti-Id MoAb 11 B 2 is “Ab 1 like Ab 3”. Therefore, it is suggested that anti-Id MoAb M 315 bears an “internal image” of the MoAb P 1-356-defined epitope on CEA.

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Anti-idiotypic (Id) antibody activity to auto and allo anti-DNA antibody in sera of 10 patients with systemic lupus erythematosus (SLE) was studied. Anti-Id antibody activity to auto anti-DNA antibody was detected in inactive phase of all cases, and it was suggested that anti-Id antibody to auto anti-DNA antibody might be closely related to the disease activity and immune regulatory system. Anti-Id antibody activity to allo anti-DNA antibody and monoclonal anti-ds DNA antibody (NE-1) was highly detected in inactive phase. We thought that the cross reactive Id may be and a restricted number of Id exists among anti-DNA antibody in sera of SLE patients.

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Urinary transforming growth factor-beta (TGF-beta) excretions were measured in 33 patients including 10 with systemic lupus erythematosus (SLE), 8 with focal glomerular sclerosis (FGS), 9 with IgA nephropathy (IgAN) and 6 with membranous nephropathy (MN) and 7 healthy subjects by enzyme-linked immunosorbent assay (ELISA) using monoclonal antibody specific for TGF-beta₁₊₂₊₃ A significantly increased urinary TGF-beta excretion was observed in FGS patients, 555.5±458.4ng/mgCr, than that of normal controls, 46.9±43.9ng/mgCr (p<0.05), and a relative increase in SLE patients, 96.4±58.2ng/mgCr, and decrease in MN patients, 24.8±13.3ng/mgCr. In contrast, there was no difference of TGF-beta excretion between IgAN patients, 54.1±37.4ng/mgCr, and normal controls. A correlation between the amount of proteinuria and TGF-beta was not found.
As has been previously demonstrated in experimental studies, TGF-beta may play a similar role in human glomerular diseases. Results obtained in this study raised the possibility that extracellular matrix (ECM) might be produced by glomerular cells in vivo under the control of TGF-beta, and that TGF-beta might act as a stimulator for the development of glomerulosclerosis.

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Effects of OK-432 on normal human monocyte functions such as phagocytosis and TNF-α and GM-CSF production as well as H₂O₂ production by neutrophils after stimulation with these cytokines were studied in vitro. TNF-α and GM-CSF levels were measured by ELISA and intracellular H₂O₂ production by flow cytometry. The results were as follows; (1) monocytes phagocytized Texas red-labeled OK-432 within 1 hr after exposure to OK-432, though TNF-α and GM-CSF were hardly ditectible at the time. (2) TNF-α levels in the medium remarkably increased approximately 3 hrs after exposure, whereas GM-CSF levels in the medium increased approximately 6 hrs after exposure to OK-432. (3) Time course of TNF-α and GM-CSF production showed different peak time distribution. GM-CSF levels, however, were much less than TNF-α levels at any time. (4) rhTNF-α and rhGM-CSF stimulated H₂O₂ production in normal human neutrophils. The rhGM-CSF levels required to produce H₂O₂ by neutrophils were higher than GM-CSF levels secreted into the medium by monocytes. We concluded that monocytes stimulated with OK-432 secreted sufficient TNF-α for neutrophils to produce H₂O₂, whereas GM-CSF secreted might function within the cytokine network rather than oxiradical production.

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A 17 year-old man was admitted to Yokohama Rosai Hospital because of severe anemia and high serum level of LDH on September 4, 1992. He was diagnosed as Evans syndrome by clinical laboratory data. On sixth day after administration of 40mg/day of Prednisolone (PSL), he was fevered up to 38°C and group O 9 Salmonella was detected from his blood. The bacteria was determined as S. enteritidis by serotype with Vi (-), O-9, H-g. Stool culture was negative. Although fever was down after administration of amikacin sulfate (AMK) and fosfomycin (FOM), he was fevered up again following of methyl-PSL pulse therapy which was done for his low platelet count (4.3×10⁴/μl) . Then aztreonam (AZT) and cefoperazone sodium (CPZ) were administered, and he had never been relapsed. As is known that healthy Salmonella carriers are gradually increased, a happens of non-typhoidal Salmonella bacteremia may be considered to occur in patients with impaired cellular immune system by basic disease or its treatment.

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We described a patient of eosinophilic fasciitis with eosinophil infiltration in the lungs. The patient was a 23 years old female who developed bilateral swollen and painful legs, and peripheral blood eosinophilia after the episode of upper respiratory infection. A wedge biopsy of the leg revealed thickned fascia and remarkable eosinophil infiltration in the perimyosium. Transbronchial lung biopsy showed significant infiltration of eosinophils in the alveoli and alveolar walls, although the chest X-ray showed only slight infiltrationshadows and pulmonary function test were within normal limits. This case was diagnosed to have eosinophilic fasciitis by the findings of bilateral swollen and painful legs, and peripheral blood eosinophilia, and the characteristic biopsy findings of the fascia. Until now eosinophilic fasciitis associated with lung involvement has not been reported. Thus, this case was of note to study a new spectrum of eosinophilic fasciitis.

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We reported a case of C7 deficiency associated with Sjögren's syndrome, Raynaud's phenomenon and anti-centromere antibody. A 54 years old woman complained of Raynaud's phenomenon, dry mouth and dry eye in 1986. She was pointed out to have keratocojunctivitis sicca, leukocytopenia, anti-centromere antibody, elevated anti DNA antibody and decreased CH 50 activity. Anti-centromere antibody and decreased CH 50 activity was persistent until the present time.
Further examination identified the presence of C7 deficiency. In the previously reported cases of C7 deficiency, only 2 SLE, 1 rheumatoid arthritis, 1 ankylosing spondylosis and 1 CREST syndrome cases were noticed.
The relationship between Sjögren's syndrome, Raynaud's phenomenon, anti-centromere antibody and C7 deficiency remains unclear in this case.

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