| First Author | Ashley SN | Year | 2019 |
| Journal | Cell Immunol | Volume | 346 |
| Pages | 103997 | PubMed ID | 31703913 |
| Mgi Jnum | J:292142 | Mgi Id | MGI:6435564 |
| Doi | 10.1016/j.cellimm.2019.103997 | Citation | Ashley SN, et al. (2019) TLR9 signaling mediates adaptive immunity following systemic AAV gene therapy. Cell Immunol 346:103997 |
| abstractText | An ongoing concern of in vivo gene therapy is adaptive immune responses against the protein product of a transgene, particularly for recessive diseases in which antigens are not presented to lymphocytes during central tolerance induction. Here we show that Toll-like receptor 9 (TLR9) signaling activates T cells against an epitope tagged mitochondria-targeted ornithine transcarbamylase (OTC) following the administration of a systemic adeno-associated virus (AAV) vector. Using a transgenic mouse model system, we demonstrate that TLR9 signaling extrinsic to T cells induces a robust cytotoxic T-cell response against the transgene and results in transgene expression loss. Overall, our results suggest that inflammation mediated by TLR9 signaling and the presence of high affinity transgene-specific T cells is important for the development of adaptive immune responses to transgene products following AAV gene therapy. |
