We next tested whether rAAV2/1-PDL-L1 or rAAV2/1-PDL-L2 could synergize with CTLA-4/Ig to improve transgene tolerance at later time points when the initial CTLA-4/Ig monotherapy was evidently not efficient alone to completely block immune sensitization against sOva. This combined strategy may indeed target two non-redundant mechanisms of immunomodulation acting www.frontiersin.org either on the APC side for CTLA-4/Ig or on the target tissue side for rAAV2/1-PD-L1 and rAAV2/1-PDL-L2. To test this possibility, groups of mice were transduced i.m. with rAAV2/1-Ova and also received at the same time either rAAV2/1-PD-L1 or rAAV2/1-PD-L2 i.m. and CTLA-4/Ig i.p. combination therapies. We then evaluated the cellular and humoral immune responses at different time points and finally evaluated the persistence of transduced muscle cells by quantification of Ova DNA and mRNA at day 80 (Figure 3) .