Expression of CD30 on T helper cells in the inflammatory infiltrate of acute atopic dermatitis but not of allergic contact dermatitis

The CD30 molecule has been proposed as a marker for a subset of CD4+CD45RO+ (memory) T cells with potent B cell helper activity producing IL-5 and IFN-gamma and as a specific marker for Th2 cells. Recently, an association has been demonstrated between elevated serum levels of soluble CD30, which is shed by CD30+ cells in vitro and in vivo, and atopic dermatitis but not respiratory atopic disorders or allergic contact dermatitis. We studied the expression of CD30 in the inflammatory infiltrate of atopic dermatitis compared with that of allergic contact dermatitis, with special regard to skin disease activity (acute vs subacute/ chronic). Biopsies were obtained from 16 patients suffering from atopic dermatitis (acute n = 6, subacute/ chronic n = 10), from 7 patients with acute allergic contact dermatitis and from 5 positive patch-test reactions. Paraffin-embedded as well as snap-frozen material was stained with anti-CD30 and anti-CD45RO mAbs according to standard procedures. Double-staining procedures for CD30CD3, CD30CD4, CD30CD45RO and CD30CD68 were also performed. Abundant CD45RO+ cells were detected both in atopic dermatitis and in allergic contact dermatitis lesions. We found scattered CD30+ cells in only one of six formalin-fixed paraffin-embedded acute atopic dermatitis biopsies, but in all of the respective snap-frozen specimens, possibly because CD30 expression on atopic dermatitis infiltrating cells is weak and sensitive to formalin fixation and paraffin embedding. CD30CD3 and CD30CD4 double staining identified CD30+ cells to be helper T lymphocytes. No significant CD30 expression (either in paraffin-embedded or in frozen material) could be found in subacute/chronic atopic dermatitis lesions or in any of the specimens of allergic contact dermatitis. The results suggest a specific regulatory function of CD30+ T cells in acute atopic dermatitis. With respect to the view that CD30 is a marker for Th2 cells, our observations confirm previous findings that Th2 cells predominate in the infiltrate particularly of acute atopic dermatitis. CD30 expression in acute atopic dermatitis but not in acute allergic contact dermatitis might be helpful in the histological differentiation of these disorders and in the further characterization of atopy patch testing.     

The allergic skin

The main cutaneous manifestation of allergy is eczema. In atopic dermatitis, the epidermal Langerhans cells express receptors for IgE and the eczematous lesions may be associated with other atopic disorders such as asthma or pollinosis. In contact dermatitis, the epidermal Langerhans' cells play the role of antigen-presenting cells; the antigens eliciting the eczematous lesions may be of occupational, vestimentary, cosmetical, therapeutical or other environmental origin. Epicutaneous test procedures enable their identification. Paraptic eczema is a concept including all the cutaneous and systemic complications of contact dermatitis.     

Regulation of the development of type 2 T-helper cells in allergy

In the last few years evidence has been accumulated to suggest that allergen-reactive type 2 T helper (Th2) cells play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils, the cellular triad involved in the allergic inflammation. Interleukin (IL)-4 production by a still unknown cell type (T-cell subset, mast cell/basophil?) at the time of antigen presentation to the Th cell is critical for the development of Th2 cells. Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and progesterone, also play a favoring role. In contrast, cytokines such as interferon-alpha, interferon-gamma, IL-12 and transforming growth factor-beta, and hormones, such as dehydroepiandrostenone, play a negative regulatory role in the development of Th2 cells. However, the mechanisms underlying the preferential activation by environmental allergens of Th2 cells in atopic subjects still remain obscure. Among the possibilities are alterations to molecular mechanisms directly involved in the regulation of IL-4 gene expression or deficient regulatory activity of cytokines that antagonize Th2 cells.     

Reversal of human allergic T helper 2 responses by engagement of signaling lymphocytic activation molecule

Allergen-specific Th2 cells accumulate at high frequencies in the skin of patients with atopic dermatitis (AD), where they contribute to the induction and maintenance of the lesions that are characteristic for the disease. Attenuation of these lesions in response to successful therapy is associated with a reduction in IL-4-producing Th2 cells and the appearance of IFN-gamma-producing Th cells. In this study, we demonstrate that engagement of the signaling lymphocytic activation molecule (SLAM) by an agonistic mAb, during allergen-specific expansion of highly polarized Th2 cell populations derived from skin biopsies of AD patients, results in the generation of stable populations of IFN-gamma-producing cells. SLAM-mediated reversal of Th cell phenotype has important biologic consequences, because supernatants of these activated, allergen-specific Th cells fail to induce IgE synthesis by purified B cells costimulated by anti-CD40 mAbs. Thus, highly polarized, allergen-specific Th2 cell populations derived from the skin of AD patients can be reversed into Th cell populations that contain IFN-gamma-producing cells and that do not support IgE synthesis. These results define a new mechanism to promote Th0/Th1 differentiation and suggest a potential role for anti-SLAM mAbs in the treatment of Th2-mediated allergic diseases.     

Membrane localisation of a UDP-sugar hydrolase, in Salmonella, is by an uncleaved N-terminal signal peptide

Many immunologic aspects of atopic dermatitis have been studied, but basic pathobiologic mechanisms of this disease remain unknown. In this study, we measured the production of interleukin-6 (IL-6) by peripheral blood T cells and monocytes from patients with atopic dermatitis in comparison to normal control subjects and patients with chronic psoriasis. We found that peripheral blood T cells isolated from patients with atopic dermatitis produced significantly higher levels of IL-6 (36.1 +/- 5.1 units/ml, n = 22) than T cells derived from either normal subjects (12.6 +/- 1.9 units/ml, n = 22) or patients with chronic psoriasis (26.7 +/- 4.1 units/ml, n = 7). T-cell activation was also measured in the patients with atopic dermatitis by soluble serum IL-2 receptor levels and were found to be significantly higher (623.7 +/- 8.1 units/ml, n = 8) than normal subjects (357.2 +/- 26.0 units/ml, n = 8). In contrast to the increased production of IL-6 by T cells in atopic dermatitis, there was no significant difference in the IL-6 production by peripheral blood monocytes derived from patients with atopic dermatitis compared to normal subjects. Thus, peripheral blood T cells derived from patients with AD spontaneously produce increased amounts of IL-6 compared to T cells from normal subjects, which may reflect the increased activation state of T cells in atopic dermatitis. These data support the concept that activated T cells or subsets of T cells may be important effector cells in mediating inflammatory activity in atopic disease.     

Blood eosinophils and serum IgE as predictors for prognosis of interferon-gamma therapy in atopic dermatitis

BACKGROUND: Interferon-gamma (IFN-gamma) therapy has been reported to be effective in atopic dermatitis. However, IFN-gamma therapy in atopic dermatitis has not yet been well established. In this study, immunologic variables were evaluated as predictors for the prognosis of IFN-gamma therapy in atopic dermatitis. METHODS: Sixty-eight atopic dermatitis patients were each treated 18 times with 2 x 10(6) units/m2 IFN-gamma. Blood IgE level, eosinophil percentage, eosinophil count, and levels of IFN-gamma, interleukin-4 (IL-4), IL-5, and IL-10 were investigated. According to clinical responses, patients were classified into three groups: patients with improved clinical severity scores of over 20% were included in group A; those with improved scores of 20% or less in group B; and those with no improvement in group C. RESULTS: Serum IgE levels and blood eosinophil percentages were the lowest in group A. Most atopic dermatitis patients with an eosinophil percentage over 9% and IgE level over 1500 IU/ml did not respond to IFN-gamma therapy. Initial IL-10 levels were the highest in group A. IL-4 levels in group A, and IL-5 and IL-10 levels in all groups were significantly decreased by IFN-gamma therapy. CONCLUSIONS: IFN-gamma therapy may be recommended for atopic dermatitis patients with blood eosinophil percentages less than 9% and serum IgE levels less than 1500 IU/ml.     

Manifestations of food allergy: evaluation and management

The term "food allergy" refers to adverse immunologic reactions to food. Food allergy is usually mediated by IgE antibody directed to specific food proteins, but other immunologic mechanisms can also play a role. The primary target organs for food allergic reactions are the skin, the gastrointestinal tract and the respiratory system. Both acute reactions (hives and anaphylaxis) and chronic disease (asthma, atopic dermatitis and gastrointestinal disorders) may be caused or exacerbated by food allergy. The foods most commonly causing these reactions in children are milk, egg, peanuts, soy, wheat, tree nuts, fish and shellfish; in adults, they are peanuts, tree nuts, shellfish and fish. The diagnosis of food allergy requires a careful search for possible causes, confirmation of the cause(s) with supporting tests, including specific tests for IgE (i.e., prick skin tests, radioallergosorbent tests) and, in some cases, oral food challenges. Treatment consists of elimination of the causal food(s) along with medical treatment, including the prompt self-administration of epinephrine in the event of a serious reaction.     

Hospital infections and their prevention in dental clinics

The normal flora is typified by the yeast-like fungi Malassezia (Pityrosporum). Successful attempts at treating patients with atopic and seborreic dermatitis, pityriasis versicolor, and psoriasis with antifungicides confirm the involvement of these fungi in the etiology and development of these diseases. In patients with various skin diseases, an immune response to M. furfur is specific. In those with psoriasis, it is characterized by the higher chemoatractant activity of polymorphonuclear leukocytes stimulated by a M. furfur extract and by the immune response of IgG antibodies with immunoreactive proteins having a molecular weight of 100-120 kD. Patients with atopic dermatitis show a hyperimmune IgE-mediated response to M. furfur, with its specific Th2-lymphocytes inducing the atopic cytokines (IL-4, IL-10) that stimulate allergic reactions to other allergens. Those with pityriasis versicolor had impaired keratinocytic pigment exchange due to azelainic acid produced by M. furfur. The cause of transformation of the yeast phase of M. furfur to the mycelial one is presumably to be changes in the composition of fatty acids of the sebaceous glands due to increased androgen concentrations.     

Relationship between interferon-gamma, interleukin-4 and IgE production of lymphocytes from hen's egg-sensitive patients

We measured in vitro interferon-gamma, interleukin-4 and IgE production of peripheral blood mononuclear cells stimulated with ovalbumin. Interferon-gamma in culture supernatants of ovalbumin-stimulated peripheral blood mononuclear cells from hen's egg- sensitive patients with atopic dermatitis was significantly higher than that of healthy children or hen's egg-sensitive patients with immediate symptoms. Furthermore, in patients with atopic dermatitis who were sensitive to hen's egg and patients with immediate symptoms, there was an inverse relationship between interferon-gamma and IgE production (r = -0.535, p <0.05), and significant correlation was found between interleukin-4 and IgE production (r = 0.802, p <0.05). For the above reasons, IgE synthesis of ovalbumin-stimulated peripheral blood mononuclear cells may be suppressed by interferon-gamma in patients with atopic dermatitis. In contrast, in patients with immediate symptoms, interleukin-4 may play a major role in the pathogenesis of increased IgE production.     

T cells subsets and cytokines in allergic and non-allergic children. II. Analysis and IL-5 and IL-10 mRNA expression and protein production

Interleukin 5 (IL-5) has an enhancing effect on IL-4 induced immunoglobulin E (IgE) synthesis. Furthermore, IL-5 plays an important role in the differentiation, recruitment, activation and survival of eosinophils. IL-10 has a downmodulating effect on interferon gamma (IFN-gamma) production and can exert strong anti-inflammatory activities. Therefore, we analysed whether differences were present in IL-5 and IL-10 mRNA expression and protein production between T cells of children with allergic and non-allergic asthma, atopic dermatitis and healthy control children. We demonstrated significant increases in IL-5 mRNA expression and protein production in different T cell fractions of children with allergic and non-allergic asthma and children with atopic dermatitis as compared to healthy controls. This indicates that IL-5 is not only involved in allergy, but also plays a role in the inflammatory process of non-allergic asthma. Interestingly, IL-10 mRNA expression by purified T cells of children with allergic and non-allergic asthma and children with atopic dermatitis was strongly decreased as compared with that of healthy controls. In the peripheral blood mononuclear cell (PBMC) fraction, IL-10 mRNA expression was comparable between the four groups. We hypothesize that this decreased T cell derived IL-10 expression results in a lack of immunosuppression of the inflammatory process in these diseases. However, a role of monocyte derived IL-10 cannot be ruled out.     

Monitoring of serologic immune parameters in inflammatory skin diseases

This paper deals with the correlation of clinical scoring and serologic markers of inflammation in atopic dermatitis and psoriasis. Serum eosinophil cationic protein (ECP), soluble interleukin-2 receptor (sIL-2R), total serum IgE, IgG and IgM anti-IgE antibodies, and IgE immune complexes were evaluated in monitoring inflammatory skin diseases such as atopic dermatitis and psoriasis. Well-established clinical activity scores were used as standards in recording skin improvement under treatment in a clinical setting. Serum ECP was found to be increased in both atopic dermatitis and psoriasis patients compared to normal controls; sIL-2R and IgE immune complexes were increased only in atopics with increased serum IgE. Anti-IgE antibodies did not show any deviation in both groups of patients. There was a significant elevation of sIL-2R and IgE immune complexes and a nonsignificant elevation of ECP in high-IgE atopics in comparison to those with normal serum IgE. In both groups of patients, there was a significant reduction of ECP and sIL-2R accompanying the improving skin condition. Serum IgE and the other immune parameters failed to respond. In contrast to other studies, serum ECP failed to correspond significantly with disease activity in our study. Our results showed measurable changes of ECP and sIL-2R for atopic dermatitis and/or psoriasis under treatment, but comparison to clinical scores remains difficult due to the different basis of the two systems. The only significant correlation was established for relative changes in sIL-2R and psoriasis area and intensity (PASI), a correlation which might be a useful approach in psoriasis.     

Cytokine production in children outgrowing hen egg allergy

BACKGROUND: Approximately 40 to 80% of egg-allergic children outgrow egg allergy after 2 to 5 years. OBJECTIVE AND METHODS: To detail the immunologic mechanisms involved in the development of tolerance to egg proteins, the balance between interleukin 4 (IL4) and interferon-gamma (IFN-gamma) synthesis in patients with active atopic dermatitis allergic to hen egg and in those outgrowing hen egg allergy was evaluated. RESULTS: A marked increase in IL4 and a decrease in IFN-gamma synthesis by peripheral blood lymphocytes following ovalbumin (OVA) specific in vitro stimulation was observed in active atopic dermatitis. In contrast, OVA-induced IL4 synthesis in patients in remission was comparable to that in normal individuals. An intriguing finding was higher production of IFN-gamma by lymphocytes from ovalbumin-insensitive patients in remission as compared to normal individuals following antigen stimulation, although cell proliferation in OVA-stimulated lymphocytes was reduced in patients during remission. CONCLUSION: OVA antigen may be capable of inducing a population of Th1-type cells to produce cytokines such as IFN-gamma, resulting in suppression of Th2-type responses, i.e. IL4 secretion. We speculate that the changes in the balance of relevant antigen-induced cytokine synthesis seen in such patients may be causally associated with the improvement in their clinical status.     

Pathogenicity and lethality of a minute intestinal fluke, Neodiplostomum seoulense, to various strains of mice

Atopy is a genetically determined disorder that affects 10%-20% of the population. Many symptoms of patients with atopy (allergic rhinitis, conjunctivitis, asthma, and anaphylaxis) result from events occurring after crosslinking of cell-bound IgE by per se innocuous environmental antigens. The frequently raised hypothesis that autosensitization can also be a pathogenetic factor in atopy, gained support by our recent demonstration of IgE antibodies against human proteins in atopic dermatitis patients. To unravel the molecular nature of IgE-defined autoantigens, we used serum IgE from atopic dermatitis patients to screen a human epithelial cDNA expression library. One of the cDNA-encoding IgE-reactive products contained 1501 bp of a 2274 bp open-reading frame finally identified by sequence analysis of two additional cDNA clones resulting from oligonucleotide screening. The IgE-defined autoantigen, designated Hom s 1, exhibited an almost complete sequence identity with a recently described antigen recognized by cytotoxic T cells of a squamous cell carcinoma patient. Purified recombinant Hom s 1 specifically bound IgE from patients with severe atopy. When used as immunogen in rabbits, recombinant Hom s 1 gave rise to an anti-serum that reacted with a cytoplasmic protein exhibiting a broad cellular and tissue reactivity (skin, lung > gastrointestinal tract > muscle, brain) and identified a 55 kDa protein in blotted serum IgE preparations. The attractive possibility remains that the Hom s 1-triggered IgE response contributes to the events resulting in allergic tissue inflammation. If so, the respective recombinant molecule may serve as a paradigmatic tool for the diagnosis and treatment of patients with "intrinsic" atopy.     

Allergy to nuts and allergy to birch

Among 527 children and young in age from 2 months to 19 years of life it has been separated the group 70 with increased specific IgE levels to hazelnuts or/and to peanuts. In them it has been determined specific IgE to pollen birch and it has been make correlation the results with the symptoms. Specific IgE has been determined immunoenzymatic Visagnost Tosse Diagnostika method. The control group stand 34 children in the same age with the infections symptoms. In the infants group--13 (59.1%) had sIgE to birch, in children 2-3 age group--15 (75%), in 406 age--8 (72.7%), in the school age--7 (87.5%) and in young > 16 age--8 (88.9%). In the control group found absence sIgE to each of examination allergens. In 5 infants in the time of the pollen birch (April 1993) it has been manifestation dyspnoea. In group 2-3 age--in 10 (45.5%) found pollinosis symptoms, 12 (60%) had asthmatic dyspnoea, 7 (35%) atopic dermatitis, 2 (10%) allergic rhinoconjunctivitis and 5 (25%) abdominal pain with concomitant dyspnoea. It has been characteristic, that never found one of clinical allergic symptoms. In group 5-6 age and 7-15 age it has been dominated atopic dermatitis (63.3% and 87.5%), pollen asthma (45.4% and 62.5%) and pollinosis (45.4% and 25%). While in young 16 age--8 (88.8%) had pollinosis, 5 (55.5%) had atopic dermatitis and pollinosis. The conclusion: 1. In children which had specific IgE to nuts increased together with age specific IgE to birch. 2. The gravely pollinosis symptoms appear in small children in 1-2 age of life, already.(ABSTRACT TRUNCATED AT 250 WORDS)     

A role for T-helper type 1 and type 2 cytokines in the pathogenesis of various human diseases

Mosmann first proposed the existence of subsets of CD4+ T cells that produce distinct types of cytokines. Native T lymphocytes (Thp cells) differentiates into either CD4+ Th1 cells that produce IL-2, IFN gamma, and lymphotoxin which promote cell-mediated immunity, or into Th2 cells that produce IL-4, IL-5, IL-6, IL-10 and IL-13, which promote antibody production and humoral immunity. These T cell subsets reciprocally regulate one another since one of the Th1 products, IFN gamma, inhibits the proliferation and functions of Th2 cells, whereas the Th2 products, IL-4 and IL-10, suppress cytokine production by Th1 cells. A distinct Th1/Th2 divergence determine resistance versus susceptibility to diseases such as leishmaniasis and toxoplasmosis in mice. In allergic diseases such as atopic dermatitis and allergic asthma, allergen-specific T cells acquired the Th2 phenotype. These Th2 cells produce IL-4, IL-5, IL-6, IL-10 and IL-13. These cytokines induce eosinophilia and an Ig class switch to IgG4 and IgE. These Th2 cells are responsible for the enhanced production of IgE antibodies. These findings indicate that Th2 cytokines play an important role in the development of allergic diseases. The importance of cell-mediated immunity, particularly donor-anti-host CTL, in mediating acute GVHD suggests that Th1 cytokines may be important in the induction of acute GVHD. To further characterize the roles of Th1 and Th2 cytokines in the development of acute GVHD, analysis of IL-2, IFN gamma, IL-4 and IL-10 cytokine genes was performed by RT-PCR on biopsied skin specimen. An increase in mRNA expression for IL-2 and IFN gamma was observed, whereas there was no significant increase in IL-4 and IL-10 mRNA. These data suggest that Th1 cytokines may be essential for the development of acute GVHD. It is apparent that Th1 cytokines are generally harmful to the maintenance of pregnancy. We have shown that Th2 cytokines are produced by maternal T lymphocytes at the maternal-fetal surface (retroplacental blood lymphocytes). This finding strengthens the hypothesis of a significant contribution of Th2 cytokines to a successful pregnancy.     

Expression of L-selectin on peripheral memory CD4+ T cells in atopic diseases

L-selectin is one of the adhesion molecules, which is known as a leukocyte homing receptor. L-selectin contributes labile rolling adhesion of leukocytes on the blood vessel wall. To elucidate characteristics of L-selectin expression on peripheral CD4+ lymphocytes in atopic diseases, flow cytometric analysis was performed. Subjects were 7 patients with atopic asthma (BA), 10 with atopic dermatitis (AD), 9 with allergic rhinitis (AR) and 10 normal adults (control). Peripheral lymphocytes in all subjects were three-color-analyzed using monoclonal antibodies. As a result, compared with the control group. BA and AD showed significantly higher proportions of L-selectin-positive memory CD4+ T cells (BA 64.0%; AD 62.0%; AR 50.9%; Control 38.0%), and significantly lower proportions of L-selectin-negative memory CD4+ T cells (BA 18.3%; AD 11.6%; AR 21.1%; Control 29.2%), respectively (reported percentages represent average values for each subject group). As previously reported. L-selectin-positive memory CD4+ T cells produce mainly Th2-type cytokines (Kanegane et al., 1996); Given these results, the present study suggests that increased Th2-like cells express L-selectin for extravasation in the process of local infiltration in atopic diseases.     

Interleukin 4, total and allergen-specific immunoglobulin E antibodies in the blood of individuals with an atopic constitution

INTRODUCTION: The recently published data suggest that atopic patients have an enhanced ability to produce IL-4, even in response to antigens other than common environmental allergens or helminthic components. This aberrant IL-4 production by Th cells may be one of the immune alterations encoded by nonMHC genes in the control of basal IgE level [1-7]. The existence of atopen-CD4+ T cell clones that have diverse repertoires might be relevant for aetiopathogenesis of atopic diseases [8-10]. Being subjected continuously to the environmental antigens (allergens), the immune system, especially T cells, is permanently activated and stimulated in response to that challenge. Due to that, substantial amount of diverse cytokines (and their soluble receptors) could be found in the serum. Accordingly, it could be expected to find raised serum IL-4 concentration in atopic persons. In this study we investigated concentrations of IL-4, total IgE and allergen-specific IgE in sera of atopic persons susceptible to pollen allergens. The main goal was to estimate whether the immunologic profile of atopics is defined by increased serum concentration of IL-4 apart from total and allergen-specific serum IgE. METHODS: Patients. We selected 9 atopic patients in the range of 19-35 years, susceptible to grass or weed pollens and suffering from allergic rhinoconjuctivitis. There were 6 females and 3 males (mean age 31.2 years). Atopic allergy was proven by clinical history, skin prick test and by means of in vitro test (positive serum allergen-specific IgE antibodies, RAST/radioallergosorbent tests [11]. As controls we randomly selected B blood donors (6 females, 2 males, mean age 31.3). Study design. The study was carried out from August till September 1995. None of selected patients had previously accomplished allergen-specific immunotherapy nor had been medicated by corticosteroids (topic or systemic) [12-15]. Selected persons were not allowed to take medications such as antihistamines, beta-2 agonists or tricyclic antidepressants at least 10 days prior to the study. We performed in vitro tests for determining concentrations of IL-4, total and pollen-specific serum IgE. Sera were sampled in the morning and were stored frozen at -20 degrees C until analysis. Determination of IL-4, total and allergen specific IgE in serum. Interleukin-4 measurement was carried out in blind fashion with an ELISA kit (Intertest-4 ELISA, Genzyme, Cambridge) according to the manufacturer's instructions. A reference curve was obtained by plotting the IL-4 concentration of several standard dilutions versus an absorbency. The determination limit was 0.045 pg/ml. For determining total serum IgE we used commercially available enzyme immunoassay (EIA Phadezym IgE PRIST, Pharmacia, Uppsala). Normal values was up to 120 IU/L (international unit per ml). Allergen specific IgE was determined by semiquantitative EIA method (RAST Phadezym, Pharmacia, Uppsala) and expressed in Phadebas RAST Unit (PRU) according to standard curve done by manufacturer. Study was carried out after approval of the Ethic Committee of our Hospital and with the obtained patients consents. For statistical analysis we used nonparametric tests (U-test and the Spearman rank correlation). For all comparisons, statistical significance was considered to be present if p < 0.05. RESULTS: Among selected patients, 4 persons had high concentration of serum IgE antibodies (RAST class 4) against grass pollens, two persons had IgE-specific (RAST, class 4) to weed pollens and 2 patients had IgE antibodies (RAST class 4) against weed and grass pollens simultaneously. RAST of class 3 was registered in the serum of one person. Registered serum total IgE, allergen-specifc IgE and IL-4 are shown in Table 1. Serum IL-4 was significantly higher in atopics (U-test, SR 43.53, p.05) as well as total IgE (ER 493, p.05). In atopics, IL-4 was not in correlation with either total or allergen-specific IgE (IL-4 versus total IgE, p = +0.190;     

IgE-induced passive sensitization of human isolated bronchi and lung mast cells

Passive sensitization of human isolated lung with serum from atopic asthmatic patients provides an opportunity to study the link between airway hyper-responsiveness and the allergic process. To directly demonstrate the role of immunoglobulin E (IgE) in the effect of the atopic serum, we have compared the effect of passively sensitizing both human bronchi and isolated lung mast cells with either serum from atopic asthmatic patients or human monoclonal IgE. Peripheral bronchi ( < 5 mm in internal diameter) were dissected out from human lung obtained at thoractomy and isometric contraction was studied in response to a variety of immunological stimuli according to the sensitization protocol. Mast cells were also isolated from human lung and histamine release was measured under similar experimental conditions. A contractile response was elicited by either the specific antigen or anti-IgE (0.6-600 ng.mL-1) but not anti-immunoglobulin G (IgG) 0.2-20 micrograms.mL-1) in airways sensitized with atopic serum (total IgE concentration of approximately 1,000 international units (IU).mL-1). The maximal contractile response to anti-IgE was 75 +/- 22% of the response to 1 mM acetylcholine. Similarly, anti-IgE released histamine from isolated lung mast cells sensitized with atopic serum up to 22.4 +/- 2% of total histamine measured within mast cells. When isolated airways or mast cells were sensitized with human monoclonal IgE (1,000 IU.mL-1), response to anti-IgE in terms of contractile response or histamine release, respectively, were not significantly different from those obtained following passive sensitization with atopic serum. Finally, the bronchial contractile response to anti-IgE depended not only on the concentration of anti-IgE but also on that of IgE (300-2,000 IU.mL-1) used to sensitize the airways. These results indicate that the effect of antigen or anti-IgE in peripheral bronchi passively sensitized with atopic serum is mimicked when sensitization is carried out directly with human monoclonal IgE.