Dynamics of antigen presentation to transgene product-specific CD4⁺ T cells and of Treg induction upon hepatic AAV gene transfer.

ABSTRACT: The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4⁺ T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8) vector expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive transfer of transgenic OVA-specific T cells. We find that that the liver-draining lymph nodes (celiac and portal) are the major sites of MHC II presentation of the virally encoded antigen, as judged by in vivo proliferation of DO11.10 CD4

SUBMITTER: Perrin GQ 

PROVIDER: S-EPMC5142511 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature