3rd EAACI Davos Meeting in Basic Immunology in Allergy and Clinical Immunology

The Swiss Institute of Allergy and Asthma Research (SIAF) and the Academy’s Immunology and Pediatric Sections organized the Davos meeting for the third time. This meeting was attended by 80 pre- and postdoctoral scientists and young European Academy of Allergology and Clinical Immunology (EAACI) members who were selected based on their recent research results. This meeting aimed to provide an up-to-date overview of the newest concepts of allergic diseases and inflammation. Through a mixture of presentations and discussions, the course intended to give postgraduate and PhD students and young researchers an opportunity to learn more about the newest insights and techniques in the pathophysiology of allergy and asthma. Peter Krammer, Patrick Holt, Kim Bottomly, David Gray, Raif Geha and Markus Manz delivered outstanding keynote lectures on innate immunity, adaptive immune responses and animal models of allergic inflammation.

In his keynote lecture, Patrick Holt (University of Perth, Australia) presented the recent advances in determining the role of environmental factors in asthma and allergy. Since the dramatic rise in allergies and asthma, scientists are constantly looking for epidemiologic evidence for this trend. Recent findings indicate that this rise has been driven by changes in the social and physical environment, and a complex interaction between these environmental factors and genetic background. The time frame over which this increase has occurred makes it implausible that they could be the result of genetic changes only [1]. Second, most of the findings indicate that these factors exert their influence during early life. A population-based birth cohort clearly confirms this and demonstrates that persistent asthma in young adults is associated with onset of wheezing at an early age and impaired lung function during childhood. In atopics and nonatopics, T-cell immunity to inhalant allergens differs both qualitatively and quantitatively. As in mice, the current concepts of the mechanisms underlying atopy include the well-known T-helper (Th)1/2 paradigm. It is generally accepted that T-cell responses in atopics are dominated by Th2 cytokines such as interleukin (IL)-4, -5 and -13, and activated Th2 cells are found in airway biopsies from atopic asthmatics [2]. During the early postnatal period, the allergen-specific Th memory is developed and the cytokine profile of these memory responses are Th2 polarized. In nonatopics, the responses are dominated by interferon (IFN)-γ in combination with IL-10. An IFN-γ deficiency was described in children with a high genetic risk for developing atopic diseases [4]. Holt first identified the inverse relationship between Th1 function (IFN-γ production) in infancy and the genetic risk for atopic disease. Attenuated IFN-γ production during the early postnatal period is a hallmark of children at risk from allergic sensitization. The degree of attenuation of IFN-γ production in children with a high genetic risk for atopy varies from a twofold reduction in peripheral blood mononuclear cell cultures, to as much as tenfold in purified T-cells.

Although these findings were confirmed by others, the precise role of IFN-γ deficiency in this life phase remains unclear. Recent results indicate that these responses frequently involve an additional Th1 component in the form of IL-10, which is produced by human Th1 and 2 clones and IFN-γ, which is a Th1 component [5]. This finding is consistent with other studies showing that older children who develop atopy have higher levels of IFN-γ production than nonatopics [6]. In a recent prospective study, Holt demonstrates a transient Th1 deficiency followed by a rebound of IFN-γ production by the end of infancy [3]. In an unselected cohort of 130 prospective analyses of tetanus toxoid vaccine-specific Th1 and 2 responses, children with an atopic family history have a Th2-skewed response at 6 and 12 months of age. This Th1 deficiency was transient and at the age of 18 months, the Th1:Th2 ratio was higher compared with those without an atopic family history. In a second study, cord blood mononuclear cells were collected from 175 children, and cytokine responses were determined after stimulation with allergens and mitogens phytohemaglutinin and staphylococcal enterotoxin B (SEB). The results indicate that, among the low IFN-γ producers, the children with the highest response rate are more likely to develop atopic diseases. They also found that the expression of atopy at 2 years of age was associated with elevated Th2 responses to SEB, in particular, IL-13 production. Taken together, these findings suggest that the Th1 deficiency of the adaptive immune system during infancy is transient and is followed by a significant rebound of the Th1 compartment, reflected by a high IFN-γ production in childhood. Holt argued that this pheno-menon may be an integral part of the atopic phenotype and that IFN-γ plays a dual role in the development of allergic diseases. On the one hand, IFN-γ antagonizes the disease process by inhibiting Th2 differentiation, but on the other hand, once sensitization has occurred it may directly or indirectly amplify a Th2-driven tissue inflammation, contributing to the persistence and severity of the disease, despite many reports on the potential protective effects of Th1 immunity. So once allergen-specific Th memory is stabilized, allergen-induced interactions can occur between Th1 and 2 pathways that are not necessarily antagonistic.

The key note lectures were followed by mini symposia in which promising young scientists presented and discussed their work. The afternoon hours were reserved for winter sports, and many EAACI junior members took advantage of the excellent snow conditions on the Jakobshorn and Parsenn slopes. After dinner, some unforgettable poster sessions were organized accompanied by desserts and followed by lengthy discussions. The casual atmosphere allowed an excellent interaction between students and professors. The third EAACI Davos Meeting was truly outstanding with regard to science, weather and social activities. Paul Van Cauwenberge, Global Allergy and Asthma European Network (GA²LEN) coordinator, announced that GA²LEN will support the Davos meetings from now on and it will be organized every year. The name ‘Davos meeting’ will be kept even if it is held in another location every second year. The 2006 Davos meeting will be organized by GA²LEN and EAACI in Garmisch-Partenkirchen (Germany) [2–6].