| First Author | Smith T | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 8 | Pages | 2713-2720 |
| PubMed ID | 28864471 | Mgi Jnum | J:251201 |
| Mgi Id | MGI:6103704 | Doi | 10.4049/jimmunol.1700427 |
| Citation | Smith T, et al. (2017) Peripheral Deletion of CD8 T Cells Requires p38 MAPK in Cross-Presenting Dendritic Cells. J Immunol 199(8):2713-2720 |
| abstractText | Peripheral tolerance mechanisms exist to prevent autoimmune destruction by self-reactive T cells that escape thymic deletion. Dominant tolerance imposed by CD4(+)Foxp3(+) T regulatory cells can actively control autoaggressive T cell responses. Tolerance mechanisms that act endogenous to the T cell also exist. These mechanisms include T cell inactivation (anergy) and deletion. A major difference between anergic T cells and T cells undergoing peripheral deletion is the capacity of the latter to still signal through MAPKs upon TCR stimulation, suggesting these signals may be required for T deletion. In this study, we used several different models of CD8 T cell deletion to investigate the contribution of MAPK activation. Using chemical inhibitors, we established that inhibition of p38, but not ERK or JNK, rescue T cells from undergoing peripheral deletion both in vitro and in vivo. Using T cell-specific murine lines genetically altered in expression of p38alpha, and mice in which p38alpha was deleted only in CD11c-expressing cells, we surprisingly found that CD8 T cell-intrinsic p38alpha activation was not responsible for increased survival, but rather that inhibition of p38alpha in the Ag-presenting dendritic cells prevented CD8 T cell deletion. |
