Eckard Hamelmann

CD8+ T cells regulate immune responses in a murine model of allergen‐induced sensitization and airway inflammation

The role of CD8+ T cells in the development of allergic airway disease is controversial. On the one hand, CD8+ T cells are known to inhibit the development of airway hyperreactivity (AHR) in murine models of asthma. In humans, IL‐10‐producing CD8+ T cells were shown to act as regulatory cells, inhibiting both proliferation and cytokine secretion of T cells. On the other hand, CD8+ T cells can promote IL‐5‐mediated eosinophilic airway inflammation and the development of AHR in animal models. To examine this, we investigated the role of CD8+ T cells during the induction of allergen‐induced AHR and demonstrated a protective effect of CD8+ T cells. Depletion of CD8+ T cells prior to the immunization led to increased Th2 responses and increased allergic airway disease. However, after development of AHR, CD8+ T cells that infiltrated the lungs secreted high levels of IL‐4, IL‐5 and IL‐10, but little IFN‐γ, whereas CD8+ T cells in the peribronchial lymph nodes or spleen produced high levels of IFN‐γ, but little or no Th2 cytokines. These data demonstrate protective effects of CD8+T cells against the induction of immune responses and show a functional diversity of CD8+ T cells in different compartments of sensitized mice.

Effect of low-dose cyclosporin a microemulsion on disease severity, interleukin-6, interleukin-8 and tumor necrosis factor alpha production in severe pediatric atopic dermatitis.

Background: The release of cytokines [interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α)] by skin cells is involved in the pathogenesis of atopic dermatitis (AD). Objective: To evaluate the effect of low-dose cyclosporin A (CyA) on clinical symptoms and cytokine secretion in severe pediatric AD. Methods: Ten children with severe AD (SCORAD index >50) were treated for 8 weeks with CyA. The initial dose of 2.5 mg/kg/day was titrated to a maximum of 5 mg/kg/day until a SCORAD reduction of ≧35% was achieved (‘treatment response’). After stopping CyA all patients entered a 4-week follow-up period. Cytokine secretion (IL-6, IL-8 and TNF-α) from patients’ PBMC was assessed by ELISA before and after CyA treatment and was compared with 18 healthy nonatopic controls. Only the data of patients, who responded to CyA and did not experience a relapse during the follow-up period, were evaluated for this paper. Results: Seven patients responded to CyA without relapse during the follow-up period. The median SCORAD index in these patients improved from 71 at baseline to 22 after CyA treatment (p < 0.001). AD patients’ PBMC produced more IL-6, IL-8 and TNF-α than PBMC of controls. Suppression of IL-6 (p < 0.05) and IL-8 (p < 0.05) production was observed after CyA treatment. TNF-α levels were unchanged by CyA in all patients. Conclusions: The reduction in severity of pediatric AD with CyA is associated with decreased production of IL-6 and IL-8, but not TNF-α by PBMC.

New visions for basic research and primary prevention of pediatric allergy: An iPAC summary and future trends

Hydrolyzed formula feeding, delayed introduction of solid food, indoor allergen avoidance, smoke and pollutants avoidance have been applied for several decades as primary preventive measures for allergic diseases. Unfortunately, some of these strategies have had no or modest success. Therefore, resources need to be focused on better understanding of the early allergic events and on interventional studies to investigate new strategies of primary and secondary prevention. Accordingly, this review summarizes the state‐of‐the‐art of genetic, immunological and clinical aspects of primary prevention of allergic diseases. Studies investigating gene‐by‐gene and gene‐by‐environment interactions suggest that prevention of allergic diseases must be tailored to the individual genetic susceptibilities (‘gene profiling’) and environmental exposures. The expanding knowledge on new T cell populations (Th17, TSLP (thymic stromal derived lymphopoietin)‐dependent ‘inflammatory Th2 cells’) is also inspiring new concepts on the origins of allergic diseases. The old concept of ‘blocking immunoglobulin G antibodies’ has been re‐appraised and it is likely to generate novel preventive and therapeutic strategies. The major task for future clinical research is to clearly define the timing of optimal exposure to potential allergens. In addition, the role of microbial products such as certain bacteria, or their components, and of helminths or their larvae at different times in early life, alone or with potential allergens, definitely need to be further investigated. The benefit of efficient allergy prevention, based on focusing resources on novel and promising research lines, will be of prime importance to both affluent countries and other parts of the world where allergy is only currently emerging.