Theme based on transplantation:
transplant loss and immune tolerance
This area aims to analyse the cellular and molecular mechanisms of acute and chronic rejection phenomena in the field of organ and cell grafts (particularly stem cells), or genes (gene therapy), while, in parallel, validating diagnostic and prognostic biomarkers. Capitalising on this information, we aim to develop a number of tools for immune tolerance induction in animal models (including primates in preclinical) and in humans.
In particular we will focus on manipulating a number of sub-populations of T and B lymphocyte effectors and dendritic cells (either autologous or allogeneic), without neglecting the close relationship of these cells with other key cells such as endothelial cells.
These themes are tackled in close cooperation with the immuno-transplantation pole via the IHU CESTI. This area is structured around 3 main themes and features 7 transversal objectives in interface with oncology :
Theme 6. Epidemiological studies of graft loss.
- Aim 6.1. Development of risk scores. Via a network of validated transplantation data (DIVAT), in association with the research team EA4275 SPHERE (bioStatistics, PHarmacoepidemiology & human SciEnces REsearch), in order to introduce personalised monitoring for this risk.
Theme 7. Cellular and humoral mechanisms acute and chronic graft injuries.
- Aim 7.1. Epidemiological studies of graft loss.
– Study of endothelial dysfunction in the context of acute and chronic rejection and consequently the identification of protective cellular molecules and pathways, toward alloAc injury. – Cellular and molecular effectors of acute and chronic humoral rejections.
Aim 7.2. Monitoring graft versus host disease (GvHD) after allotransplantation of stem cells.
– Study of the role of dendritic cells, lymphoid effectors (T, NK cells) and cytokines in GvHD.
– Assessment of the impact of the polymorphism of HLA and KIR molecules in GvHD.
- Aim 7.3. Identification and validation of new biomarkers of tolerance. – Characterisation of mechanisms of the immune tolerance in cohorts of tolerant patients and animal models. – Validation of candidate biomarkers in operationally tolerant patient cohorts, in chronic rejection. – Validation of blood markers at 3 months and 1 year after the transplantation compared to biopsy tissue markers.
Theme 8. Immunointervention and cellular therapies
- Aim 8.1. Immunosuppression by costimulatory and inflammatory cytokines blockade. – Tolestim study: blockade of the CD28 costimulatory pathways by an antagonistic CD28 monovalent agent. – Targeting of T cell memories by Ac anti IL-15.
- Aim 8.2. Cellular immunosuppression. – Use of autologous dendritic cells: FP7 program « The One Study ». – Induction of central tolerance by mixed chimerism.
- Aim 8.3. Restorative or regenerative cellular therapies. – Assessment of xenotransplantation strategies with porcine islets of Langerhans on primates : “XenoThera” project. – Use of allogeneic skin cells in the framework of major cutaneous defects or burns. – Liver repair based on differentiated induced stem cells in hepatocytes .