- Dr. Michel Y. Braun, Principal Investigator
- Université Libre de Bruxelles, Brussels, Belgium
- Mechanisms of Graft Destruction in the Absence of Cognate Recognition between the Graft and T Cells
The majority of alloreactive CD4 T cells directly recognise allogeneic MHC/peptide complexes expressed by the cells of transplanted organs. CD4 T cells can also recognise donor antigens processed by recipient APC and indirectly presented to T cells as peptides in the binding groove of recipient MHC molecules. Though the participation of alloreactive T cells sensitised by the indirect pathway of allorecognition in graft rejection is well documented, their effector function in this process is unclear. It also remains to identify the nature of recipient APC capable of stimulating indirect pathway T cells within the graft and to demonstrate that such interaction is sufficient to promote the destruction of transplanted tissues. Our project will examine the mechanisms that ensure the specificity of tissue destruction in a murine TcR transgenic model where rejection occurs in the absence of cognate recognition between the graft and T cells. More specifically, we shall identify the type of APC capable of stimulating indirect pathway T cells within the graft. APC tested for their stimulatory capacities will include bone-marrow-derived immature dendritic cells, aortic endothelial cells and blood-derived fibrocytes. We shall also study the effector mechanisms of tissue destruction promoted by indirect pathway T cells by using antibody treatment, as well as a genetic approach, to neutralise the function of various lymphokines.