| First Author | Uhl M | Year | 2009 |
| Journal | Cell Death Differ | Volume | 16 |
| Issue | 7 | Pages | 991-1005 |
| PubMed ID | 19229247 | Mgi Jnum | J:164191 |
| Mgi Id | MGI:4830857 | Doi | 10.1038/cdd.2009.8 |
| Citation | Uhl M, et al. (2009) Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8+ T cells. Cell Death Differ 16(7):991-1005 |
| abstractText | Cross-presentation of cell-associated antigen is important in the priming of CD8(+) T-cell responses to proteins that are not expressed by antigen-presenting cells (APCs). In vivo, dendritic cells are the main cross-presenting APC, and much is known regarding their ability to capture and process cell-associated antigen. In contrast, little is known about the way death effector pathways influence the efficiency of cross-priming. Here, we compared two important mechanisms of programmed cell death: classical apoptosis, as it occurs in wild-type (WT) fibroblasts, and caspase-independent cell death, which occurs with increased features of autophagy in Bax/Bak(-/-) fibroblasts. We assessed virally infected WT and Bax/Bak(-/-) fibroblasts as a source of cell-associated antigen. We found that immunization with cells undergoing autophagy before cell death was superior in facilitating the cross-priming of antigen-specific CD8(+) T cells. Strikingly, silencing of Atg5 expression inhibited priming. We interpret this to be a novel form of 'immunogenic death' with the enhanced priming efficiency being a result of persistent MHC I cross-presentation and the induction of type I interferons. These results offer the first molecular evidence that catabolic pathways, including autophagy, influence the efficiency of cross-priming. We predict that targeting the autophagy cascade may provide a therapeutic strategy for achieving robust cross-priming of viral and tumor-specific CD8(+) T cells. |
