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Background: H1 antihistamines increase safety during allergen-specific immunotherapy and might influence the outcome because of immunoregulatory effects. Objective: We sought to analyze the influence of 5 mg of levocetirizine (LC) on the safety, efficacy, and immunologic effects of ultrarush honeybee venom immunotherapy (BVIT). Method: In a double-blind, placebo-controlled study 54 patients with honeybee venom allergy received LC or placebo from 2 days before BVIT to day 21. Side effects during dose increase and systemic allergic reactions (SARs) to a sting challenge after 120 days were analyzed. Allergen-specific immune response was investigated in skin, serum, and allergen-stimulated T-cell cultures. Results: Side effects were significantly more frequent in patients receiving placebo. Four patients receiving placebo dropped out because of side effects. SARs to the sting challenge occurred in 8 patients (6 in the LC group and 2 in the placebo group). Seven SARs were only cutaneous, and 1 in the placebo group was also respiratory. Difference of SARs caused by the sting challenge was insignificant. Specific IgG levels increased significantly in both groups. Major allergen phospholipase A2-stimulated T cells from both groups showed a slightly decreased proliferation. The decrease in IFN-γ and IL-13 levels with placebo was not prominent with LC, whereas IL-10 levels showed a significant increase in the LC group only. Decreased histamine receptor (HR)1/HR2 ratio in allergen-specific T cells on day 21 in the placebo group was prevented by LC. Conclusions: LC reduces side effects during dose increase without influencing the efficacy of BVIT. LC modulates the natural course of allergen-specific immune response and affects the expression of HRs and cytokine production by allergen-specific T cells. [Copyright &y& Elsevier]

The restart of the meiotic cycle in Drosophila depends on both the controlled expression of Polo kinase and a protein called Matrimony (Mtrm), which binds to and physically inactivates Polo. [ABSTRACT FROM AUTHOR]

Surfactant protein A (SP-A) and transforming growth factor-β1 (TGF-β1) have been shown to modulate the functions of different immune cells and specifically to inhibit T lymphocyte proliferation. The aim of the present study was to elucidate whether the Smad signaling pathway, which is activated by TOF-β1, also plays a role in SP-A-mediated inhibition of CD4+ T lymphocyte activation. Recombinant human SP-A1 expressed in Chinese hamster ovary cells [rSP-A1m (mammalian)], but not recombinant Baculovirus-derived rSP-A1hyp (hydroxyproline-deficient), suppressed T lymphocyte proliferation and IL-2 mRNA expression. To test whether SP-A induced Smad signaling, a Smad3/4-specific reporter gene was transfected in primary human CD4+ T lymphocytes. Only rSP-A1m, but not rSP-A1hyp, induced Smad-specific reporter genes, Srnad2 phosphorylation. and Smad7 mRNA expression. The effect of rSP-A1m was mediated through the TGF-βII and could be antagonized by anti-TGF-β1 neutralizing antibodies and sTGF-βRII. Western blot and ELISA analysis revealed that rSP-A1m, but not rSP-A1hyp, contained TGF-β1. TGFβ1 was responsible for the differences in inhibition of CD4β1 lymphocyte proliferation and activation of the Smad signaling pathway between rSP-A1hyp and rSP-A1hyp. After acidification, native SP-A. obtained from patients with alveolar proteinosis, also induced Smad signaling in human CD4+ T lymphocytes leading to an increased inhibition of T lymphocyte proliferation. thus indicating the presence of inactive, latent TGF-β1 in native SP-A samples. Association between SP-A and latent TGF-β1 provides a possible novel mechanism to regulate TGF-β1 -mediated inflammation and fibrosis reactions in the lung but also leads to possible misinterpretation of immune-modulator functions of SP-A. Monitoring of SP-A preparations for possible TGF-β1 is essential. [ABSTRACT FROM AUTHOR]

Specific immune suppression and induction of tolerance are essential processes in the regulation and circumvention of immune defence. The balance between allergen-specific type 1 regulatory (Tr1) cells and T helper (Th) 2 cells appears to be decisive in the development of allergy. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals. In contrast, there is a high frequency of allergen-specific interleukin-4 (IL-4)-secreting T cells in allergic individuals. Allergen-specific immunotherapy can induce specific Tr1 cells that abolish allergen-induced proliferation of Th1 and Th2 cells, as well as their cytokine production. Tr1 cells utilize multiple suppressor mechanisms, such as IL-10 and transforming growth factor-β (TGF-β) as secreted cytokines and various surface molecules, such as cytotoxic T-lymphocyte antigen 4 and programmed death-1. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors, which depend on CD28 costimulation. IL-10 inhibits CD28 tyrosine phosphorylation, preventing the binding of phosphatidylinositol 3-kinase p85 and consequently inhibiting the CD28 signalling pathway. In addition, IL-10 and TGF-β secreted by Tr1 cells skew the antibody production from immunoglobulin E (IgE) towards the non-inflammatory isotypes IgG4 and IgA, respectively. Induction of antigen-specific Tr1 cells can thus re-direct an inappropriate immune response against allergens or auto-antigens using a broad range of suppressor mechanisms. [ABSTRACT FROM AUTHOR]

Background: The role of regulatory T cells has been widely reported in the suppression of T-cell activation. A dysfunction in CD4+CD25+ T-regulatory cell–specific transcription factor FoxP3 leads to immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome, often associated with atopic dermatitis. Increasing the number and activity of regulatory T cells in affected organs has been suggested as a remedy in various inflammatory diseases, including allergy. Objective: To determine the presence and function of regulatory T cells in atopic dermatitis. Methods: Immunohistochemistry of lesional atopic dermatitis skin and control skin conditions was used to demonstrate regulatory cells and cytokines in situ. The role of effector and regulatory T cells as well as their specific cytokines in apoptosis in human keratinocyte cultures and artificial skin equivalents was investigated. Results: Human T-regulatory type 1 cells, their suppressive cytokines, IL-10 and TGF-β, as well as receptors for these cytokines were significantly expressed, whereas CD4+CD25+FoxP3+ T-regulatory cells were not found in lesional and atopy patch test atopic dermatitis or psoriasis skin. Both subsets of regulatory T cells suppress the allergen-specific activation of TH1 and TH2 cells. In coculture and artificial skin equivalent experiments, subsets of T-regulatory cells neither induced keratinocyte death nor suppressed apoptosis induced by skin T cells, TH1 cells, IFN-γ, or TNF-α. Conclusion: A dysregulation of disease-causing effector T cells is observed in atopic dermatitis lesions, in association with an impaired CD4+CD25+FoxP3+ T-cell infiltration, despite the expression of type 1 regulatory cells in the dermis. [Copyright &y& Elsevier]

Background: Allergic asthma typically shows activated, allergen-specific CD4+ T cells in the early phase and airway remodeling in the late phase of the disease. Although TGF-β plays a crucial role in airway remodeling, it is only marginally induced in CD4+ T cells in the early allergen-dependent activation of the immune system. Objective: To elucidate the transition between early- and late-phase events, we investigated the role of activin A, a close family member of TGF-β. Methods: Activin A and TGF-β1 levels were measured systemically in the serum and in CD4+ T cells of asthmatic patients, as well as locally in the lung. Results: Activin A serum levels were increased in patients with severe asthma compared with levels in patients with moderate asthma and healthy control subjects, whereas all patients showed significantly increased TGF-β1 serum levels independent of disease severity. In T cells only patients with moderate asthma showed increased activin A mRNA expression, whereas TGF-β1 expression was equal to that seen in healthy subjects. Accordingly, ovalbumin sensitization in a mouse model of allergic asthma could induce activin A mRNA expression, but not TGF-β1 expression, in the lung. Immunohistochemistry of mice and human specimens revealed an abundant expression of activin A by infiltrating lymphocytes and structural cells of the lung. Although TGF-β1 more potently enhanced proliferation and Smad 2/3–dependent reporter genes in fibroblasts, activin A was capable of inducing TGF-β1 and vice versa. Conclusion: Activin A provides a link between acute allergen-specific T-cell responses and chronic TGF-β1–mediated airway remodeling in asthma. [Copyright &y& Elsevier]

The identification of T regulatory (TReg) cells as key regulators of immunologic processes in peripheral tolerance to allergens has opened an important era in the prevention and treatment of allergic diseases. Both naturally occurring CD4+CD25+ TReg cells and inducible populations of allergen-specific IL-10–secreting TR1 cells inhibit allergen-specific effector cells in experimental models. Allergen-specific TReg cell responses contribute to the control of allergic inflammation in several ways. Skewing of allergen-specific effector T cells to a TReg phenotype appears to be a crucial event in the development of a healthy immune response to allergens and successful outcome in allergen-specific immunotherapy. The increased levels of IL-10 and TGF-β produced by TReg cells can potently suppress IgE production while simultaneously increasing the production of the noninflammatory antibody isotypes IgG4 and IgA, respectively. TReg cells directly or indirectly suppress effector cells of allergic inflammation, such as mast cells, basophils, and eosinophils, and contribute to remodeling in asthma and atopic dermatitis. In addition, mediators of allergic inflammation that trigger cyclic AMP–associated G protein–coupled receptors, such as histamine receptor 2, might play a role in peripheral tolerance mechanisms against allergens. Current strategies for drug development and allergen-specific immunotherapy exploit these observations with the potential to provide cure for allergic diseases. [Copyright &y& Elsevier]

Histamine, originally considered as a mediator of acute inflammatory and immediate hypersensitivity responses has also been demonstrated to affect chronic inflammation and regulate several essential events in the immune response. On the other hand, various cytokines control histamine synthesis, release and expression of histamine receptors (HRs). The cells involved in the regulation of immune response and hematopoiesis express HRs and also secrete histamine, which can selectively recruit the major effector cells into tissue sites and affect their maturation, activation, polarization and effector functions leading to chronic inflammation. Histamine, acting through its receptor type 2, positively interferes with the peripheral antigen tolerance induced by T regulatory cells in several pathways. Histamine also regulates antigen-specific Th1 and Th2 cells, as well as related antibody isotype responses. The diverse effects of histamine on immune regulation are due to differential expression and regulation of four HRs and their distinct intracellular signals. In addition, differences in affinities of these receptors are highly decisive on the biological effects of histamine and agents that target HRs. This article highlights the findings leading to a change of perspective in histamine immunobiology. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Specific immunotherapy is a common treatment of allergic diseases and could potentially be applied to other immunologic disorders. Despite its use in clinical practice, more defined and safer allergy vaccine preparations are required. Differences between epitopes of IgE that recognize the 3-dimensional structure of allergens and T cells that recognize linear amino acid sequences provide a suitable tool for novel vaccine development for specific immunotherapy. Objective: The aim of the study was to delete B-cell epitopes and prevent IgE crosslinking, but to preserve T-cell epitopes by fusion of 2 major allergens of bee venom because of a change in the conformation. Methods: By genetic engineering, we produced a fusion protein composed of the 2 major bee venom allergens: phospholipase A2 (Api m 1) and hyaluronidase (Api m 2). Results: The Api m [1/2] fusion protein induced T-cell proliferation and both TH1-type and TH2-type cytokine responses. In contrast, IgE reactivity was abolished, and profoundly reduced basophil degranulation and type 1 skin test reactivity was observed. Pretreatment of mice with Api m [1/2] fusion protein significantly suppressed the development of specific IgE as well as other antibody isotypes after immunization with the native allergen. Conclusion: The novel fusion protein of 2 major allergens bypasses IgE binding and mast cell/basophil IgE FcεRI crosslinking and protects from IgE development. [ABSTRACT FROM AUTHOR]

Specific immunotherapy (SIT) represents the only curative treatment of allergy and is, therefore, of particular interest for immunological and pharmacological research. The current understanding of immunological mechanisms underlying SIT focuses on regulatory T cells (T regs), which balance Th1 and Th2 effector functions. This ensures that allergens are recognized, but tolerated by the immune system. There is clear evidence that SIT restores the disturbed balance of T regs and effector cells in allergic patients. Current efforts are focused to improve SIT regimens to make them more applicable in atopy and asthma. The current review provides an overview on the mechanisms of SIT and possible adjuvant treatment strategies on the background of the T reg concept. [ABSTRACT FROM AUTHOR]

Background: T cells are key regulators of immunologic disease parameters. However, their contribution to the process of tissue remodeling is ill defined. In the present study, we investigated gene expression of allergy-characteristic, IL-4-rich T cell cDNAs to monitor expression of genes that might participate in the pathogenesis of allergic diseases. Methods: cDNAs of freshly isolated and restimulated CD4+ T cells from patients with allergic asthma (AA) or atopic dermatitis (AD) and healthy subjects were analyzed on Nylon membrane-based DNA arrays. Three patients were selected for an allergy-characteristics T cell phenotype with high IL-4 expression (AA) or IL-13 expression (AD). Results: Several gene families such as the TGF-Β family, chemokines and chemokine receptors were found to be upregulated. Matrix metalloproteinases and their inhibitors were also found to be expressed in an enhanced manner. Furthermore, factors regulating tissue turnover such as fibroblast growth factors and neurotrophic as well as vasoactive factors were found be expressed at a higher level in allergic patient compared to healthy donors. Conclusion: The present study reveals and confirms genes relevant for allergy and highlights an approach to applying a DNA array technique for diagnostic discrimination of allergic diseases. [ABSTRACT FROM AUTHOR]

Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces large amounts of interleukin-5. In this study, we examined 60 patients with idiopathic eosinophilia. Sixteen patients had circulating T cells with an aberrant immunophenotype that, in most cases, were associated with different forms of skin inflammation. The abnormal T cells produced large amounts of interleukin-5, which may have increased eosinophil differentiation in the bone marrow of these patients.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Specific immunotherapy (SIT) is an efficient treatment of allergic diseases to defined allergens. Despite being used in clinical practice since early in this century, more rational and safer regimens are required, because SIT is faced with the risk of anaphylaxis and standardization problems of allergen-extract-based treatments. A better understanding of the pathogenesis of allergy and of the mechanisms of SIT has led to various approaches to overcome these problems. Knowledge of the influence of IgE-facilitated antigen presentation on allergen-specific Th2 responses increased the efforts to generate non-IgE-binding allergens. The current principal approach to allergen modification is to modify B cell epitopes in order to prevent IgE binding and effector cell cross-linking while preserving T cell epitopes to retain the capacity of inducing tolerance. In this way, the modified allergen will be directed to T cells by a phagocytosis/pinocytosis-mediated antigen uptake mechanism, bypassing IgE cross-linking and IgE-dependent antigen presentation. Accordingly, a differential regulation of allergen-specific T cell cytokine patterns and IgE:IgG production was demonstrated by modifications of the three-dimensional structure of allergens because of linearity in T cell epitopes and conformation dependence in B cell epitopes. In this context, chemically modified allergen extracts with low IgE-binding capacity have been developed to reduce anaphylactic side effects since the early 1980s. The progress of recombinant techniques for producing allergens and allergen derivatives has led to a dramatic improvement in the ability of developing novel vaccines for the treatment of allergy. This has enabled mutation or deletion of decisive amino acids in B cell epitopes and fractionation or oligomerization of allergens by genetic engineering as fruitful approaches to generate hypoallergenic vaccines. Moreover, non-IgE-binding short T cell epitope peptides and single-amino-acid-altered peptide ligands represent potential candidates for future SIT.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In allergic inflammations of the skin, the pivotal role of CD45RO+ (memory/effector) T cells expressing the cutaneous lymphocyte–associated antigen (CLA) was demonstrated. In both atopic dermatitis (AD) and contact dermatitis (CD), T cells specific to skin–related allergens were confined to the CLA+ T cell population. Our research was aimed to further characterize these T cells in AD. Methods: CD4+ and CD8+ subsets of CLA+ CD45RO+ T cells were purified from peripheral blood of AD patients and healthy control individuals. We studied, in vivo activation patterns, cytokine profiles, immunoglobulin isotype regulation and the influence of these cells on eosinophil survival and apoptosis. Results: The CLA+ CD45RO+ T cells represent an in– vivo–activated memory/effector T cell subset as shown by surface expression of activation markers, spontaneous proliferation and a lower activation threshold via TCR/CD3 triggering. These cells contain and spontaneously release high amounts of preformed IL–5 and IL–13 but only very little IL–4 and IFN–γ in their cytoplasm, as demonstrated by intracellular cytokine staining immediately after purification. Moreover, CLA+ memory/ effector T cells induce IgE production in B cells and enhance eosinophil survival by inhibiting eosinophil apoptosis in AD. In comparison, the CLA– population represents a resting memory T cell fraction, induces rather IgG4 in B cells and does not show any effect on eosinophil survival and apoptosis. Conclusion: Our results indicate that in–vivo–activated both CD4+ and CD8+ memory/effector T cells with skin–homing property play a specific and decisive role in the pathogenesis and exacerbation of AD. In contrast, resting memory T cells of atopic individuals retain normal, nonallergic immune functions. [ABSTRACT FROM AUTHOR]

Background: Induction of specific unresponsiveness (tolerance/anergy) in peripheral T cells and recovery by cytokines from the tissue microenvironment represent two key steps in specific immunotherapy (SIT) with whole allergen or antigenic T cell peptides. Methods: Antigen-specific T cell responses and molecular mechanisms of T cell inactivation were investigated during conventional SIT, T cell epitope peptide immunotherapy and natural exposure to bee venom in allergic and hyperimmune individuals. Results: T cell unresponsiveness, initiated by autocrine action of IL-10, is characterized by suppressed proliferative and cytokine responses. The unresponsive T cells can be reactivated by different cytokines that may mimic the microenvironmental cytokine influence. IL-10 initiates peripheral tolerance by blocking the CD28 costimulatory signal in T cells. Coprecipitation experiments reveal that upon stimulation CD28 and IL-10 receptor are physically associated in T cells. Accordingly, IL-10 binding to its receptor inhibits CD28 tyrosine phosphorylation, the initial step of the CD28 signaling pathway. This leads to inhibition of phosphatidylinositol 3-kinase p85 binding to CD28. IL-10 only affects T cells that receive a stimulation with low numbers of triggered T cell receptors and that require costimulatory signals by CD28. Conclusion: These data demonstrate the pivotal role of autocrine IL-10 and the interaction of its receptor with CD28 in the induction of T cell tolerance as an immunoregulatory mechanism controlling antigen-specific T cell responses.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Focuses on a study which explained the existence and activation of CD8+ T cells in eczema lesions contributing to immunoglobulin E production and eosinophil survival and development, chronicity and exacerbation of atopic dermatitis (AD). Classification of AD as a skin disease; Role played by T cells in both AD and contact dermatitis; Way in which additional evidence for in vivo activation of CLA+ T cells appears.

Demonstrates that the recombinant Bet v 1 fragments induced proliferation of PBMC from birch pollen-allergic patients comparable to the rBet v 1 wild type, indicating that both fragments contain most of the Bet v 1-specific T cell epitopes. Characteristics of the major birch pollen allergen Bet v 1; Results from the immunization of rabbits and mice with purified rBet v 1 fragments; Effectiveness of hypoallergenic rBet v 1 fragments as vaccines.

Summary Heterogeneity of lymphocyte populations demonstrates the diversity of cellular immune responses and provide a better understanding of the immune system. CD3+ CD8+ T cells exhibit a low CD8 expressing (CD8low ) population in flow cytometric analysis of peripheral blood T cells. In healthy donors, this population consists of 0·2–7·0% of all CD8 T cells. The majority of the CD8low T cell population showed an elevated expression of CD25, CD45RA, and CD95L, and low levels of CD28, CD62L and CD45RO. Circulating CD8low T cells resemble cytotoxic effector cells because they express cytolytic mediators and are able to execute cytotoxicity. A restricted T cell receptor profile with increased Vβ9, Vβ14 and Vβ23 expression was observed and the CD8low T cell population contain Epstein–Barr virus-specific T cells. Therefore, the CD8low population represent a subset of activated CD8 effector T cells, resulting most probably from a continous and/or balanced immune response to intracellular pathogens. [ABSTRACT FROM AUTHOR]

Abstract: Interleukin (IL)-10 is an essential suppressive cytokine and plays a key role in peripheral T cell tolerance to allergens, autoantigens, transplantation antigens and tumor antigens. However, the molecular mechanisms of direct T cell suppression by IL-10 are not fully understood. Here, we demonstrate that IL-10 directly inhibits CD2 signaling in T cells. T cell stimulation via CD2 alone induces activation and proliferation, when endogenous IL-10 sources are eliminated from cultures. IL-10 utilizes the src-homology-2 domain containing tyrosine phosphatase (SHP-1) to directly suppress T cell activation. The role of SHP-1 in IL-10-mediated suppression of CD2 co-stimulation on T cells is demonstrated by using dominant-negative SHP-1 over-expressing T cells and silencing endogenous SHP-1 by small inhibitory RNA. Findings are confirmed using both SHP-1-deficient mice and IL-10-deficient mice. CD2-induced proliferation is suppressed by exogenous IL-10 in IL-10-deficient, but not SHP-1-deficient murine T cells. In conclusion, SHP-1-mediated inhibition of CD2 signaling represents a novel mechanism for direct T cell suppression by IL-10. [Copyright &y& Elsevier]

Histamine is a potent bioamine with multiple activities in various pathological and physiological conditions. In addition to its well-characterised effects in the acute inflammatory and allergic responses, histamine regulates several aspects of antigen-specific immune response development. Histamine affects the maturation of dendritic cells and alters their T cell-polarising capacity. Histamine also regulates antigen-specific T helper 1 and T helper 2 cells, as well as related antibody isotype responses. Apparently, diverse effects of histamine on immune regulation are because of differential expression of four types of histamine receptors and their distinct intracellular signals. [Copyright &y& Elsevier]

Recently we have shown that T-cell-mediated keratinocyte apoptosis plays a key pathogenetic role in the formation of eczematous dermatitis. Spongiosis, the histologic hallmark of eczematous dermatitis, is characterized by impairment of cohesion between epidermal keratinocytes. It is conceivable that the intercellular junction of keratinocytes is an early target of apoptosis-inducing T cells. In this study, we demonstrate that the induction of keratinocyte apoptosis is accompanied by a rapid cleavage of E-cadherin and loss of coimmunoprecipitated β-catenin. In situ examination of E-cadherin expression and cellular distribution in acute eczematous dermatitis revealed a reduction in keratinocyte membrane E-cadherin in areas of spongiosis. In contrast, the in vitro and in vivo expression of desmosomal cadherins during early apoptosis remained unchanged. Therefore, induction of keratinocyte apoptosis by skin-infiltrating T cells, subseqent cleavage of E-cadherin, and resisting desmosomal cadherins suggests a mechanism for spongiosis formation in eczematous dermatitis. [ABSTRACT FROM AUTHOR]

A subgroup of patients with atopic dermatitis are known to have normal serum total immunoglobulin E levels, undetectable specific immunoglobulin E, and negative skin prick tests towards allergens. This form of the disease has been termed nonallergic atopic dermatitis. In this study, we found that, among 1151 chronic atopic dermatitis patients, about 10% had normal serum immunoglobulin E levels with no evidence for immunoglobulin E sensitization. We investigated immunologic mechanisms of patients with “allergic” and “nonallergic” atopic dermatitis using peripheral blood and skin biopsy samples. Our data suggest that T cells are likely involved in the pathogenesis of both forms of atopic dermatitis. Skin T cells equally responded to superantigen, staphylococcal enterotoxin B, and produced interleukin-2, interleukin-5, interleukin-13, and interferon-γ in both forms of the disease. Interleukin-4, however, was not detectable in the skin biopsies of both atopic dermatitis types and was secreted in very low amounts by T cells cultured from the skin biopsies. Moreover, skin T cells from nonallergic atopic dermatitis patients expressed lower interleukin-5 and interleukin-13 levels compared with allergic atopic dermatitis patients. Accordingly, T cells isolated from skin biopsies of atopic dermatitis, but not from the nonallergic atopic dermatitis, induced high immunoglobulin E production in cocultures with normal B cells that was mediated by interleukin-13. In addition, B cell activation with high CD23 expression was observed in the peripheral blood of atopic dermatitis, but not nonallergic atopic dermatitis patients. These data suggest, although high numbers of T cells are present in lesional skin of both types, a lack of interleukin-13-induced B cell activation and consequent immunoglobulin E production in nonallergic atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: The cause of persistent eosinophilia and the hypereosinophilic syndrome is unknown. Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces large amounts of interleukin-5, a cytokine required for the growth and differentiation of eosinophils. We examined T-cell surface markers, rearranged T-cell–receptor genes, and in vitro production of cytokines by T cells from patients with idiopathic eosinophilia. Methods: The expression of surface molecules on T cells was measured by flow cytometry. Cytokine expression was measured by enzyme-linked immunosorbent assay, flow cytometry, and immunohistochemical analysis. To identify dominant (clonal) rearrangements of the T-cell receptor within the lymphocyte population, Southern blot analysis (β chain) and the polymerase chain reaction (γ chain) were performed according to standard protocols. Results: Among 60 patients with idiopathic eosinophilia, 16 had circulating T cells with an aberrant immunophenotype. In each of these patients, the abnormal immunophenotype was unique. Evidence of clonal rearrangements of the T-cell receptor was obtained in 8 of the 16 patients. In most instances, the abnormal T cells expressed large amounts of surface proteins associated with T-cell activation (the α chain of the interleukin-2 receptor and the HLA-DR antigen). Moreover, the aberrant T cells produced large amounts of interleukin-5 in vitro. Conclusions: Clonal populations of abnormal T cells producing interleukin-5 occur in some patients with idiopathic eosinophilia. (N Engl J Med 1999;341:1112-20.) [ABSTRACT FROM AUTHOR]