| First Author | Lorenzi S | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 9 | Pages | 5142-50 |
| PubMed ID | 21441457 | Mgi Jnum | J:173116 |
| Mgi Id | MGI:5009749 | Doi | 10.4049/jimmunol.1004163 |
| Citation | Lorenzi S, et al. (2011) Type I IFNs control antigen retention and survival of CD8alpha(+) dendritic cells after uptake of tumor apoptotic cells leading to cross-priming. J Immunol 186(9):5142-50 |
| abstractText | Cross-presentation is a crucial mechanism for generating CD8 T cell responses against exogenous Ags, such as dead cell-derived Ag, and is mainly fulfilled by CD8alpha(+) dendritic cells (DC). Apoptotic cell death occurring in steady-state conditions is largely tolerogenic, thus hampering the onset of effector CD8 T cell responses. Type I IFNs (IFN-I) have been shown to promote cross-priming of CD8 T cells against soluble or viral Ags, partly through stimulation of DC. By using UV-irradiated OVA-expressing mouse EG7 thymoma cells, we show that IFN-I promote intracellular Ag persistence in CD8alpha(+) DC that have engulfed apoptotic EG7 cells, regulating intracellular pH, thus enhancing cross-presentation of apoptotic EG7-derived OVA Ag by CD8alpha(+) DC. Notably, IFN-I also sustain the survival of Ag-bearing CD8alpha(+) DC by selective upmodulation of antiapoptotic genes and stimulate the activation of cross-presenting DC. The ensemble of these effects results in the induction of CD8 T cell effector response in vitro and in vivo. Overall, our data indicate that IFN-I cross-prime CD8 T cells against apoptotic cell-derived Ag both by licensing DC and by enhancing cross-presentation. |
