Humoral and cellular immune responses communicate with each other via Fc receptors (FcR) expressed on various hematopoietic cells. Recent studies on several FcR knockout mice demonstrated pivotal roles of an IgG/FcγR system in the regulation of immune responses and the onset of hypersensitivity. The γ subunit of FcR is an essential component of the complex and is required for both receptor assembly and signal transduction. FcR γ chain-deficient mice have lost the functional expression of FcεRI, FcγRI, and FcγRIII and are unable to mount several types of hypersensitive reactions, including the skin Arthus reaction. In contrast, FcγRII-deficient mice exhibit augmented humoral immune responses and IgG-mediated anaphylaxis reactions. Thus, the regulatory system of murine hypersensitive responses involves both positive and negative signaling through FcR. In B cells, FcγRIIb modulates membrane Ig-induced Ca²⁺ mobilization by inhibiting Ca²⁺ influx through phosphorylation of its immunoreceptor tyrosine-based inhibition motif and recruitment of cytoplasmic phosphatases. Elucidation of the detailed mechanisms of negative regulatory signaling in the inflammatory effector cells by FcγRIIb as well as several groups of potent inhibitory molecules expressed on such cells should be valuable in the development of novel therapeutic procedures for allergic disorders.

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Signaling lymphocytic activation molecule (SLAM; CDw150) is a 70 kDa glycoprotein. Signaling lymphocytic activation molecule is constitutively expressed on memory T cells, CD56⁺ T cells, a subset of T cell receptor γδ⁺ cells, immature thymocytes and, at low levels, on a proportion of peripheral blood B cells. Signaling lymphocytic activation molecule is rapidly upregulated on all T and B cells after activation. Engagement of SLAM by F(ab′)₂ fragments of an anti-SLAM monoclonal antibody (mAb A12) enhances antigen-specific T cell proliferation. In addition, mAb A12 was directly mitogenic for T cell clones and activated T cells. T cell proliferation induced by mAb A12 is independent of interleukin (IL)-2, IL-4, IL-12 and IL-15, but is cyclosporin A sensitive. Ligation of SLAM during antigen-specific T cell proliferation resulted in upregulation of interferon (IFN)-γ production, even by allergen-specific T helper cell (Th) 2 clones, whereas the levels of IL-4 and IL-5 production were only marginally affected. The mAb A12 was unable to induce IL-4 and IL-5 production by Th1 clones. Costimulation of skin-derived Der P 1-specific Th2 cells from patients with atopic dermatitis via SLAM resulted in the generation of a population of IFN-γ-producing cells, thereby reverting their phenotype to a Th0 pattern. Signaling lymphocytic activation molecule is a high-affinity self ligand mediating homophilic cell interaction. In addition, soluble SLAM enhances both T and B cell proliferation. Collectively, these data indicate that SLAM molecules act both as receptors and ligands that are not only involved in T cell expansion but also drive the expanding T cells during immune responses into the Th0/Th1 pathway. This suggests that signaling through SLAM plays a role in directing Th0/Th1 development.

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The epithelium of the airway has considerable capacity to undergo repair. These repair processes are responsible for maintaining and restoring function after injury of the airways, which likely occurs often as a result of infectious, toxic or other exposures. However, repair processes need not be fully effective. Inadequate repair can take a number of forms and may result in metaplasia, hyperplasia or fibrotic scarring. It is likely that repair processes that lead to tissue disruption play an important role in the chronic airways diseases, such as asthma and bronchitis. Through delineation of these processes, it may become feasible to target therapeutic interventions in order to achieve more effective maintenance of tissue structure.

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We used flow cytometry to investigate the expression of α4β7 integrin on peripheral blood CD4⁺ T cells stimulated with αs-casein, one of the major allergens in milk allergy, in patients with milk-induced enterocolitis. In the active state of the disease, the levels of α4β7 integrin on αs-casein-stimulated CD4⁺ T cells, as well as the numbers of positive cells, were higher than in the age-matched control. Upon outgrowing milk allergy, α4β7 integrin levels decreased to the same levels as in the healthy control. The proliferative responses of peripheral blood mononuclear cells to αs-casein in the active state did not differ from those in the outgrown state, suggesting that the expression of α4β7 integrin on milk allergen-activated T cells is a marker of the activation state leading to the pathogenesis of milk-allergic enterocolitis.

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The occupational uses of latex gloves may be associated with allergic rhinitis. Hypersensitivity to latex has been shown to be IgE-mediated. However, late nasal responses to latex have not been reported. The present report describes a clinical and immunological study of a dental nurse with work-related rhinitis induced by the use of latex gloves. To examine whether late nasal symptoms were associated with infiltration of T cells and eosinophils and also with preferential expression of T helper 2 (Th2) cell type cytokine mRNA, nasal biopsies were performed before and 24 h after latex provocation and were processed for immunohistology and in situ hybridization. Latex induced early and late nasal responses. After latex provocation, the numbers of T cells and eosinophils were markedly increased compared with number on the control day. In situ hybridization confirmed Th2 type cytokine mRNA expression at 24 h after latex provocation. These results suggest that latex provokes IgE-mediated early and late nasal responses and that late nasal symptoms are associated with an infiltration of T cells and eosinohils and the production of Th2 type cytokines.

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Interstitial lung disease (ILD) can be separated into two groups: (i) that in which the causes are known; and (ii) that in which the etiologies have not been determined. Meanwhile, complement is essential for the inflammatory response and complement systems have been recognized as factors involved in organizing ILD. In the present study we investigated whether there were any differences in complement-related membrane proteins on lymphocytes and alveolar macrophages in bronchoalveolar lavage fluids (BALF) between different ILD. Bronchoalveolar lavage fluid samples were obtained from 12 patients and eight healthy individuals. Bronchoalveolar lavage fluid cells were incubated with monoclonal antibodies (mAbs) against C3b/C4b receptor (CR1), C3bi receptor (CR3), membrane cofactor protein (MCP) and decay accelerating factor (DAF) and were then labeled with fluorescein isothiocyanate-conjugated anti-mouse IgG. Cells were analyzed using a flow cytometer. The results demonstrate for the first time that CR3 and DAF are elevated on alveolar macrophages, and that MCP and DAF are increased on BALF lymphocytes in sarcoidosis. The possible roles of complement-related membrane proteins in the pathogenesis of immune processes that are ongoing in sarcoidosis are still obscure, but our results may provide some useful information on the mechanisms underlying sarcoidosis.

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The effects of corticosteroids on bone mass in patients with bronchial asthma (BA) are still controversial. To elucidate whether steroid administration may influence bone mineral content (BMC) and bone mineral density (BMD) in women with BA, a longitudinal study was designed for adult female asthmatics receiving long-term steroid therapy. We measured whole body BMC and lumbar BMD by dual energy X-ray absorptiometry in 23 women with BA and compared the results with those from 17 age-matched controls. Both patient and control groups were followed up for at least 1 year (mean (± SD) observation period 94 ± 33 weeks). We divided the asthmatic patients into two groups on the basis of the mode of steroid administration: (i) group A consisted of 10 patients with low dose oral steroid administration (prednisolone 5-10 mg daily); and (ii) group B consisted of 13 patients with low dose beclomethasone dipropionate (BDP) inhalation therapy (BDP 400-800 mg daily). There were no significant differences in both baseline values and changes of BMC and BMD among the three groups. These results demonstrate that asthmatic patients show normal bone mass and that both low dose steroid administration and BDP inhalation do not significantly affect BMC in patients with BA over the period studied. We suggest that appropriate steroid use does not augment bone mineral loss in asthmatics.

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Using immunoblotting and densitometer techniques, we followed the levels of IgE and IgG₄ antibodies to Dermatophagoides farinae antigen in the sera of 12 asthmatic children during immunotherapy, repeated injections of house dust extract, for 2 years. The symptoms of asthma were reduced or disappeared by the 6th month after starting immunotherapy in 12 children. Two years later, RAST scores to house dust and D. farinae in each child were still 4 or 5. The levels of IgE antibodies to Der fII in all cases did not change drastically. IgE antibodies to higher molecular weight antigens (Der fI, fIII, fIV etc.) developed in some cases, suggesting that repeated injections of crude extract tended to induce IgE antibodies to alternative molecules in patients. The IgG₄ antibody to Der fII increased in 10 cases, while that to Der fI increased in three of 12 cases, indicating that production of IgG₄ antibodies to mite antigens started and expanded with repeated injections of house dust extract. The amount of induced IgG₄ antibodies to Der fI and Der fII was not enough to inhibit the immunoblot reaction of IgE antibodies to these molecules.

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To analyze the development of antigen-specific IgE in infants and its clinical usefulness, the levels of IgE antibodies against egg white (f1) and cows' milk (f2) in 33 sera from cord blood, 118 sera from atopic dermatitis (AD) infants and 197 sera from non-atopic control infants were measured by using the CAP radioallergosorbent test (RAST) fluoro enzyme immunoassay (FEIA) system, which has a detection limit of 0.15 Ua/mL for f1 and 0.20 Ua/mL for f2. No antigen-specific IgE was detected in cord blood, whereas in infants younger than 6 months of age, 38.5% of AD infants and 6.6% of the non-atopic controls showed IgE against f1 (≥0.70 Ua/mL) and 14.3 and 4.0%, respectively, showed low levels (0.15-0.70 Ua/mL) of the IgE. When the cut-off point for positive versus negative f1 RAST was set at 0.15 or 0.35 Ua/mL instead of 0.70 Ua/mL, the significance of the difference in f1 RAST-positive and -negative proportions between atopic and non-atopic infants did not change. Repeated examination of f1 RAST revealed later positive conversion in the majority of AD patients, with no detectable or very low levels (0.15-0.35 Ua/mL) of f1-specific IgE. In infants at 6 months of age or older, 44.4 and 12.0% of AD patients and non-atopic controls, respectively, showed IgE against f1 (≥0.70 Ua/mL) and 37.1 and 22.6%, respectively, showed low levels (0.15-0.70 Ua/mL) of the IgE. These results suggest that f1 RAST at a concentration of 0.15 Ua/mL or higher has diagnostic value for egg allergy in AD infants, especially in infants younger than 6 months of age. The f1 RAST should be examined repeatedly in AD infants with low levels of IgE against f1. Similar results were obtained for f2-specific IgE, but there was a significant decrease in the specificity when the cut-off point was set at 0.20 Ua/mL.

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The total number of new attendant patients diagnosed as having atopic dermatitis at our dermatology out-patient clinic during the 7 year period from 1989 to 1995 was 10 156. Patients from each year during this period were divided into eight age groups. The birth month and the month of first visit for each age group was obtained in average of 7 years. Only for subjects aged <1 year was there a definite tendency for higher birth numbers in autumn and lower birth numbers in spring. The percent birth rate for subjects <1 year of age was significantly higher in October and November and significantly lower in March and May in comparison with the expected percent birth rates calculated on the basis of birth months of the Japanese population. Similarly, patients aged <1 year, 1-2 and 3-5 years showed a tendency for higher numbers of first visits in spring and, in addition, patients aged <1 year showed a tendency for smaller numbers of first visits in summer. At school and college ages, between 6 and 20 years of age, a steep increase of first visits was observed in March and a smaller increase of first visits was observed between July and August. We investigated whether the distribution of birth month for subjects aged <1 year was statistically significant. The percent first visiting month was significantly higher in March and April and lower between July and October in comparison with the expected percentage first visiting month. We speculated that the uneven distribution of birth month was a reflection of a more marked distortion observed in the distribution of the month of first visit. The mean age at first visit (6.24 months) explains the difference between first visiting month and birth month. There were no definite social reasons for the increase in the number of first visits in spring for subjects aged <1 year. Therefore, the uneven distribution of the month of first visit for subjects aged <1 year could probably be the result of climatic effects.

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We report on a case in which five consecutive exacerbations of asthma were monitored by following serum eosinophil cationic protein (ECP) levels. The serum ECP level correlated well with each exacerbation and tended to increase even before the exacerbations of asthma became apparent. This case shows that serum levels of ECP can be useful markers of disease activity and may also be predictive markers for acute exacerbation.

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A 24-year-old female patient with chronic dry cough, without wheezing and other symptoms, was diagnosed as atopic cough variant asthma (CVA) sensitized with house dust (HD) mite. To investigate the effect of a leukotriene (LT) receptor antagonist (pranlukast hydrate, ONON 450 mg/day), cough score, respiratory function, cough receptor sensitivity to capsaicin, airway inflammation evaluated by hypertonic saline inhalation and airway reactivity to histamine were studied before and after treatment for 4 weeks. Furthermore, the effect of a LT receptor antagonist on HD allergen-induced bronchoconstrictive and cough responses was investigated. Treatment with a LT receptor antagonist resulted in disappearance of cough, improvement of respiratory function, decrease in eosinophil percentage in induced sputum and increase in capsaicin and histamine threshold. Although bronchoprovocation with HD extract induced an immediate bronchoconstriction followed by cough responses before treatment, inhibition of both bronchoconstrictive and cough responses was observed after treatment. These results suggest that LT is involved in the mechanism of cough in this patient with atopic CVA.

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