Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

Role of Der p 1–specific B cells in immune tolerance during 2 years of house dust mite–specific immunotherapy

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Human NK1 and NK2 subsets determined by purification of IFN-gamma-secreting and IFN-gamma-nonsecreting NK cells

The in vivo existence of human NK cell subsets similar to Th1 and Th2 cells was demonstrated in freshly isolated IFN-gamma-secreting and IFN-gamma-nonsecreting NK cells. The IFN-gamma-secreting NK subset showed a typical cytokine pattern with predominant expression of IFN-gamma, but almost no IL-4, IL-5 and IL-13. In contrast, the IFN-gamma-nonsecreting NK subset was composed of IL-4, IL-5 and IL-13-producing NK cells. Short-time stimulation or 2 weeks of in vitro differentiation of NK cells led to distinct patterns of cytokine production similar to freshly-purified IFN-gamma (+) or IFN-gamma (-) NK cell subsets. NK cells stimulated with IL-12 produced increased levels of IFN-gamma and decreased levels of IL-4. In contrast, stimulation of NK cells with IL-4 inhibited IFN-gamma, but increased IL-13 production. Freshly-purified IFN-gamma (+) and IFN-gamma (-) or in vitro differentiated NK1 and NK2 subsets showed similar cytotoxicity to K562 cells. These results demonstrate that circulating NK cells retain effector subsets in humans with distinct cytokine profiles and may display different inflammatory properties.     

Development and characterization of DNAzyme candidates demonstrating significant efficiency against human rhinoviruses

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Suppression of the immune system by oral glucocorticoid therapy in bronchial asthma

The effect of systemic glucocorticoid therapy on immune parameters was studied in patients with bronchial asthma. Patients were divided into two groups: 1) those receiving oral glucocorticoid; 2) control patients who did not receive systemic glucocorticoid treatment. The glucocorticoid dose varied between 5 and 70 mg per day. Patients had been taking oral therapy for at least 1 year. Glucocorticoid treatment was associated with an increased frequency of respiratory tract infections. Therefore, we need to define immune parameters which may predict an increased risk of infections. In this study, we analyzed several surface markers on lymphocytes and monocytes by flow cytometry. A significant reduction of the ratio of peripheral blood CD4⁺ to CD8⁺ T cells was associated with the administration of oral glucocorticoids. Furthermore, the expression of the HLA-DR molecule on monocytes was reduced in patients with systemic glucocorticoid therapy compared to control patients. Moreover, the capacity to elaborate cytokines by peripheral blood mononuclear cells upon stimulation was greatly reduced after exposure to glucocorticoids in vivo and in vitro. In addition, the humoral immune response was affected, because reduced IgG, IgM, and IgA levels were observed in patients receiving oral glucocorticoids. These results indicate that systemic glucocorticoid treatment in patients with bronchial asthma is associated with cellular and humoral immunosuppression which results in an increased risk of bacterial and viral infections.     

Cytokine network and dysregulated apoptosis in atopic dermatitis

Activation and skin-selective homing of peripheral blood memory/effector T cells and effector functions in the skin represent sequential immunological events in the pathogenesis of atopic dermatitis (AD). T cells infiltrating the skin utilize the cutaneous lymphocyte-associated antigen (CLA) and other receptors to recognize and cross the vascular endothelium. In the peripheral blood of AD patients, both CD4⁺ and CD8⁺ subsets of CLA+CD45RO⁺ T cells are in an activated state with high CD25, HLA-DR, and CD40- ligand expression. They express upregulated Fas and Fas-ligand and undergo activation-induced apoptosis. After homing to skin these T cells form dermal infiltrates which play a key role in the pathogenesis of the disease. Skin-infiltrating T cells in AD are protected from activation-induced cell death, although they express both Fas and Fas-ligand. They are protected from apoptosis by cytokines such as IL-2, IL-4, and IL-15 and extracellular matrix components such as fibronectin and transferrin. CLA⁺, skin-homing T cells may play a role in peripheral blood eosinophilia and hyper IgE production by high IL-5 and IL-13 expression, respectively. These T cells secrete IFN-γ in the skin, which upregulates Fas on keratinocytes and renders them susceptible to apoptosis. Keratinocyte apoptosis is induced by Fas-ligand, either soluble or expressed on the surface of T cells, leading to eczema formation. Here we discuss the mechanisms of skin-selective T cell homing and activation, and emphasize the concept of dysregulated apoptosis of T cells, eosinophils, and keratinocytes as essential pathogenetic episodes in AD and other eczematous disorders.     

Food and drug allergy,and anaphylaxis in EAACI journals (2018)

The European Academy of Allergy and Clinical Immunology (EAACI) supports three journals: “Allergy,” “Pediatric Allergy and Immunology (PAI),” and “Clinical and Translational Allergy (CTA).” One of the major goals of EAACI is to support health promotion in which prevention of allergy and asthma plays a critical role and to disseminate the knowledge of allergy to all stakeholders including the EAACI junior members. This paper summarizes the achievements of 2018 in anaphylaxis, and food and drug allergy. Main topics that have been focused are anaphylaxis, mechanisms of food allergy (FA), epidemiology of FA, food allergens, diagnosis of FA, prevention and control of FA, FA immunotherapy, drug allergy, and political agenda.     

EAACI Biologicals Guidelines—dupilumab for children and adults with moderate-to-severe atopic dermatitis

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based), its cost-effectiveness and long-term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed.