A: Immunity/Tolerance

Research Area A is developing concepts to modulate immune mechanisms at the xenograft-host interface. A1 will test the hypotheses that: i) SLA class-I deficiency with additional downregulation of SLA class-II and/or transgenic expression of hPD-L1 will result in tissues with particularly low immunogenicity; and ii) clinically suitable donor-recipient combinations can be defined by SLA-HLA matching. A2 will develop strategies of local immunomodulation delivered either by recombinant adeno-associated viral vectors (rAAV), micro-RNAs, small hairpin (sh) RNAs, or by genetic modification of the donor animal to support long-term survival of cardiac xenografts. A3 and A5 will synergistically address mechanisms of the instant blood-mediated inflammatory reaction (IBMIR) induced by intraportal islet cell transplantation and test strategies to overcome them in unique ‘humanised’ mouse models. A4 will characterise the functional peculiarities of xenoreactive regulatory T cells (Treg) and establish protocols for Treg-mediated tolerance induction, e.g. by expression of xenospecific chimeric antigen receptors (CARs).