FIGURE 7.

MHCII gene therapy to induce Treg-mediated tolerance to vascularized transplants. Transduction of BM-derived APCs from recipient mice (H-2^k) with the IAb.RV (retro IA^b) vector leads to IA^b peptides (pep) presented on MHCII^k heterodimers. These MHCII/peptide complexes participate in the thymic differentiation of IA^b-specific Tregs (GT Tregs). Self-Tregs would differentiate on self-MHCII peptides/MHCII complexes. In these animals, transplanted hearts from B6, but not from third-party BALB/c donors, provide IA^b signals for the in situ activation of GT Tregs via the direct (D) or indirect (I) presentation pathways. In turn, locally activated GT Tregs repress the entire Th1 antigraft alloresponse (spreading tolerance) and prevent rejection.