Development of new tests: Background, objectives and overall strategy In order to implement novel tolerance induction protocols in the clinical arena, we need to develop diagnostic tests able to identify in a retrospective or prospective manner those patients in whom tolerance can be or has been successfully induced. Even in well-defined experimental models, tolerance induction is rarely successful in 100% of the animals. In non-human primates the success rate decreases even further. In humans, the extended immunological experience of transplant recipients already before transplantation (i.e. heterologous immunity leading to an increased memory lymphocyte pool, including donor-reactive memory T cells), the frequent use of pre-injured organs from elderly and brain-dead donors (resulting in enhanced immunogenicity and incidence of chronic rejection) and the development of post-transplant infections all influence the risk of acute and chronic transplant rejection and probably also the threshold for tolerance induction. In this context, the establishment of immunological and molecular profiles predicting the success or failure of tolerance induction appears as a priority for the success of the RISET project as a whole. The major interest of such tests would be to minimise the risk of novel tolerance inducing principles and immunosuppression weaning during clinical trials of tolerance induction. The main objectives of WP1 are therefore: Development of assays for the: •· definition of immunological pre-transplant constellations identifying patients that are not suitable for a particular tolerance induction protocol (definition of high-risk patients before transplantation). •· early identification of failure of tolerance induction, possibly before graft deterioration occurs (definition of negative predictors early after transplantation). •· early demonstration of tolerance after induction therapy (definition of early positive predictors of success after transplantation) •· harmful injury/tolerisation of the anti-microbial immune response (definition of safety markers). •· Identification of tolerance state markers in long term stable recipients under immunosuppressive therapy. For further information please download the list of available assays below. | 
