INTEGRATION: youth welfare and sustainable development in Switzerland

In Switzerland with its 7.3 million inhabitants, about 200,000 people are working in the agricultural sector managing 66,000 farms. Between 1990 and 2000, the number of agricultural employees shrunk by 50,000 and more than 22,000 agrarian businesses were abandoned – mostly smallscale farms with less than 3 ha. The Emmental region is a part of Switzerland characterized by a high share of agriculture. Compared to other regions the proportion of rural inhabitants is still relatively high, the decline of farms is therefore below the figures of the rest of Switzerland. Nevertheless, as an effect of the structural change also in rural regions, the remaining farmers depend more and more on additional incomes and are looking for extra work in different branches. Although the Emmental region is one of the economically poor marginal regions of Switzerland, it has a multitude of strengths: besides the intact landscape and numerous natural resources the inhabitants have a strong liaison to their culture and traditions. The family structures are essentially still in good order and the social network is functioning. Based on these strengths, the project INTEGRATION aims at three main targets: * Providing space for living and developing on a qualified farm with system-therapeutic and socialpedagogic support for socially deprived children and adolescents from urban centres such as Berne, Basel and Lucerne. * Offering places of care creates innovative and sustainable supplementary earnings for the farming families in an economically unfavourable mountain area. * At the political level, a new quality of the relation between ‘city’ and ‘country’ evolves by bringing together different cultures and exchanging ideas and experiences. INTEGRATION is a social youth-welfare project with a strong liaison with the economic sector. The well-being of the involved children, adolescents and partner families comes first but with its connections to economic and ecological aspects INTEGRATION has also become a typical project in the field of sustainable rural development. This may have led to the invitation of the representatives of the project to participate in the preparatory workshop in Vorden (The Netherlands), April 2004. They had the opportunity to present and discuss the philosophy of the project INTEGRATION and its results during the last eight years. As an innovative project in the field of social youth welfare in Switzerland, INTEGRATION was also asked for a contribution to the publication ‘Farming for Health’. Although there are quite a lot of activities in this field, the term ‘Farming for Health’ is neither widely known nor used in Switzerland yet. After the preparatory workshop, the project team discussed an appropriate translation into (Swiss) German: the best working title was found in ‘Landwirtschaft und soziale Wohlfahrt’. It will be a challenge for the future to determine a term that meets most of the requirements of the then involved organizations. The first part of this contribution gives a short overall description of activities in Switzerland, while the project INTEGRATION with its targets, activities and results is described in the second par

T Cells Isolated from Positive Epicutaneous Test Reactions to Amoxicillin and Ceftriaxone are Drug Specific and Cytotoxic

In order to investigate the function of T cells in cutaneous adverse drug reactions, skin-derived T cells were analyzed in two patients with a drug-induced exanthem. Skin biopsy specimens were obtained from positive epicutaneous test reactions to amoxicillin and ceftriaxone. Immunohistochemical analysis revealed that the majority of the cell infiltrate in both biopsy specimens was composed of activated T cells, of which some expressed perforin. By limiting dilution 36 amoxicillin-specific and 10 ceftriaxone-specific T cell clones were raised. All of these T cell clones expressed CD4/T cell receptor αβ. Cytokine analysis after antigen stimulation of the seven best proliferating T cell clones (four specific for amoxicillin and three for ceftriaxone) revealed that these cells secrete high amounts of interleukin-5 and mostly lower or no amounts of tumor necrosis factor α, interleukin-4, and interferon-γ. A part of these CD4+ T cell clones were cytotoxic, i.e., two selected ceftriaxone-specific T cell clones killed target cells after antigen stimulation. The amoxicillin-specific T cell clones failed to show drug-specific cytotoxicity, but killed target cells in the presence of concanavalin A, indicating a principal ability to be cytolytic. In correlation with the in situ expression of perforin on T cells, the ceftriaxone-specific T cell clones also expressed perforin in vitro. In conclusion, a substantial part of the T cells in drug-induced epicutaneous test reactions are drug specific and are composed of a heterogeneous cell population. Drug-specific T cells producing interleukin-5 may contribute to eosinophilia, whereas cytotoxic CD4+ T cells may account for tissue damage. These data underline the role of T cells in delayed-type cutaneous adverse drug eruptions and drug-induced epicutaneous test reactions

HLA-restricted, processing- and metabolism-independent pathway of drug recognition by human alpha beta T lymphocytes.

T cell recognition of drugs is explained by the hapten-carrier model, implying covalent binding of chemically reactive drugs to carrier proteins. However, most drugs are nonreactive and their recognition by T cells is unclear. We generated T cell clones from allergic individuals specific to sulfamethoxazole, lidocaine (nonreactive drugs), and cef-triaxone (per se reactive beta-lactam antibiotic) and compared the increase of intracellular free calcium concentration ([Ca2+]i) and the kinetics of T cell receptor (TCR) downregulation of these clones by drug-specific stimulations. All drugs tested induced an MHC-restricted, dose- and antigen-presenting cell (APC)-dependent TCR downregulation on specific CD4(+) and CD8(+) T cell clones. Chemically nonreactive drugs elicited an immediate and sustained [Ca2+]i increase and a rapid TCR downregulation, but only when these drugs were added in solution to APC and clone. In contrast, the chemically reactive hapten ceftriaxone added in solution needed > 6 h to induce TCR downregulation. When APC were preincubated with ceftriaxone, a rapid downregulation of the TCR and cytokine secretion was observed, suggesting a stable presentation of a covalently modified peptide. Our data demonstrate two distinct pathways of drug presentation to activated specific T cells. The per se reactive ceftriaxone is presented after covalent binding to carrier peptides. Nonreactive drugs can be recognized by specific alphabeta+ T cells via a nonconventional presentation pathway based on a labile binding of the drug to MHC-peptide complexes