| First Author | Kenna TJ | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 2 | Pages | 598-606 |
| PubMed ID | 19995901 | Mgi Jnum | J:159425 |
| Mgi Id | MGI:4442572 | Doi | 10.4049/jimmunol.0900032 |
| Citation | Kenna TJ, et al. (2010) Targeting antigen to diverse APCs inactivates memory CD8+ T cells without eliciting tissue-destructive effector function. J Immunol 184(2):598-606 |
| abstractText | Memory T cells develop early during the preclinical stages of autoimmune diseases and have traditionally been considered resistant to tolerance induction. As such, they may represent a potent barrier to the successful immunotherapy of established autoimmune diseases. It was recently shown that memory CD8+ T cell responses are terminated when Ag is genetically targeted to steady-state dendritic cells. However, under these conditions, inactivation of memory CD8+ T cells is slow, allowing transiently expanded memory CD8+ T cells to exert tissue-destructive effector function. In this study, we compared different Ag-targeting strategies and show, using an MHC class II promoter to drive Ag expression in a diverse range of APCs, that CD8+ memory T cells can be rapidly inactivated by MHC class II+ hematopoietic APCs through a mechanism that involves a rapid and sustained downregulation of TCR, in which the effector response of CD8+ memory cells is rapidly truncated and Ag-expressing target tissue destruction is prevented. Our data provide the first demonstration that genetically targeting Ag to a broad range of MHC class II+ APC types is a highly efficient way to terminate memory CD8+ T cell responses to prevent tissue-destructive effector function and potentially established autoimmune diseases. |
